Author: "Lattante S" - Searchworks@Jio Institute Digital Library Search Results

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208 results on '"Lattante S"'

1. Induced pluripotent stem cell production (CSSi019-A)(14432) from an asymptomatic subject carrying a expansion of C9orf72 gene

Author: Ruotolo, G, D'Anzi, A, Giovenale, A, Giacometti, C, Ferrari, D, Vulcano, E, D'Asdia, C, Lattante, S, Sabatelli, M, Codazzi, F, Consalez, G, Marano, M, Di Lazzaro, V, Pennuto, M, Vescovi, A, Rosati, J, Ruotolo, G., D'Anzi, A., Giovenale, A. M. G., Giacometti, C., Ferrari, D., Vulcano, E., D'Asdia, C., Lattante, S., Sabatelli, M., Codazzi, F., Consalez, G., Marano, M., Di Lazzaro, V., Pennuto, M., Vescovi, A., Rosati, J., Ruotolo, G, D'Anzi, A, Giovenale, A, Giacometti, C, Ferrari, D, Vulcano, E, D'Asdia, C, Lattante, S, Sabatelli, M, Codazzi, F, Consalez, G, Marano, M, Di Lazzaro, V, Pennuto, M, Vescovi, A, Rosati, J, Ruotolo, G., D'Anzi, A., Giovenale, A. M. G., Giacometti, C., Ferrari, D., Vulcano, E., D'Asdia, C., Lattante, S., Sabatelli, M., Codazzi, F., Consalez, G., Marano, M., Di Lazzaro, V., Pennuto, M., Vescovi, A., and Rosati, J.
Abstract: One of the genetic mutations most associated with the onset of amyotrophic lateral sclerosis, both in sporadic and familial cases, is the expansion of the C9orf72 gene. The presence of more than 30 repeats (GGGGCC) correlates with uncertain ALS symptomatology. Here we collected a dermal biopsy from a subject carrying 36 hexanucleotide repeats and reprogrammed it into an induced pluripotent stem cell line. Despite the number of repeat elements, the subject had no symptoms at the age of the biopsy (76 years), thus resulting in a healthy carrier of the mutation
Published: 2024

2. Generation of induced pluripotent stem cells (CSSi017-A)(12862) from an ALS patient carrying a repeat expansion in the C9orf72 gene

Author: Ruotolo, G, D'Anzi, A, Casamassa, A, Mazzoni, M, Ferrari, D, Lombardi, I, Carletti, R, D'Asdia, C, Torrente, I, Frezza, K, Lattante, S, Sabatelli, M, Pennuto, M, Vescovi, A, Rosati, J, Ruotolo, G., D'Anzi, A., Casamassa, A., Mazzoni, M., Ferrari, D., Lombardi, I., Carletti, R. M., D'Asdia, C., Torrente, I., Frezza, K., Lattante, S., Sabatelli, M., Pennuto, M., Vescovi, A. L., Rosati, J., Ruotolo, G, D'Anzi, A, Casamassa, A, Mazzoni, M, Ferrari, D, Lombardi, I, Carletti, R, D'Asdia, C, Torrente, I, Frezza, K, Lattante, S, Sabatelli, M, Pennuto, M, Vescovi, A, Rosati, J, Ruotolo, G., D'Anzi, A., Casamassa, A., Mazzoni, M., Ferrari, D., Lombardi, I., Carletti, R. M., D'Asdia, C., Torrente, I., Frezza, K., Lattante, S., Sabatelli, M., Pennuto, M., Vescovi, A. L., and Rosati, J.
Abstract: Genetic expansions of the hexanucleotide repeats (GGGGCC) in the C9orf72 gene appear in approximately 40% of patients with familial ALS and 7% of patients with sporadic ALS in the European population, making this mutation one of the most prevalent genetic mutations in ALS. Here, we generated a human induced pluripotent stem cell (hiPSC) line from the dermal fibroblasts of a patient carrying a 56-repeat expansion in an ALS disease-causing allele of C9orf72. These iPSCs showed stable amplification in vitro with normal karyotype and high expression of pluripotent markers and differentiated spontaneously in vivo into three germ layers.
Published: 2024

3. Generation of induced pluripotent stem cells (CSSi017-A)(12862) from a patient carrying a repeat expansion in the C9orf72 gene and with amyotrophic lateral sclerosis

Author: Ruotolo, G., primary, D'Anzi, A., additional, Casamassa, A., additional, Mazzoni, M., additional, Ferrari, D., additional, Lombardi, I., additional, Carletti, R.M., additional, D'Asdia, C., additional, Torrente, I., additional, Frezza, K., additional, Lattante, S., additional, Sabatelli, M., additional, Pennuto, M., additional, Vescovi, A.L., additional, and Rosati, J., additional
Published: 2024
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4. Analysis of STMN2 CA repeats in italian ALS patients shows no association

Author: Doronzio, Paolo Niccolo', Lattante, Serena, Marangi, Giuseppe, Martello, Francesco, Conte, A., Bisogni, G., Bernardo, D., Patanella, A. K., Meleo, Emiliana, Zollino, Marcella, Sabatelli, Mario, Doronzio P. N., Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Martello F., Meleo E., Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), Doronzio, Paolo Niccolo', Lattante, Serena, Marangi, Giuseppe, Martello, Francesco, Conte, A., Bisogni, G., Bernardo, D., Patanella, A. K., Meleo, Emiliana, Zollino, Marcella, Sabatelli, Mario, Doronzio P. N., Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Martello F., Meleo E., Zollino M. (ORCID:0000-0003-4871-9519), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by a complex interaction of genetic and environmental factors. Recently, a polymorphic intronic CA repeat in STMN2 gene has been proposed as risk factor for ALS. The presence of long/long CA genotype, especially if one allele had 24 CA, was reported to be significantly associated with the disease in a cohort of sporadic ALS patients. We tested an Italian cohort of 366 ALS patients and 353 healthy controls and we found no association between CA length and ALS risk.
Published: 2023

5. Induced pluripotent stem cell production (CSSi019-A)(14432) from an asymptomatic subject carrying a expansion of C9orf72 gene

Author: Ruotolo, G., D’Anzi, A., Giovenale, A.M.G., Giacometti, C., Ferrari, D., Vulcano, E., D’Asdia, C., Lattante, S., Sabatelli, M., Codazzi, F., Consalez, G., Marano, M., Di Lazzaro, V., Pennuto, M., Vescovi, A., and Rosati, J.
Published: 2024
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6. Generation of an induced pluripotent stem cell line (UCSCi001-A) from a patient with early-onset amyotrophic lateral sclerosis carrying a FUS variant

Author: Martello, F., Lattante, S., Doronzio, P. N., Conte, A., Bisogni, G., Orteschi, D., Pirozzi, F., Sabatelli, M., Zollino, M., Marangi, G., Martello F., Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Marangi G. (ORCID:0000-0002-6898-8882), Martello, F., Lattante, S., Doronzio, P. N., Conte, A., Bisogni, G., Orteschi, D., Pirozzi, F., Sabatelli, M., Zollino, M., Marangi, G., Martello F., Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), and Marangi G. (ORCID:0000-0002-6898-8882)
Abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons. We generated patient-derived-induced Pluripotent Stem Cells (iPSCs), from an ALS patient affected by an early-onset and aggressive form of the disease, carrying a missense pathogenic variant in FUS gene. We reprogrammed somatic cells using an established Sendai virus protocol and we obtained clones of iPSC. We confirmed their stemness and further generated embryoid bodies, showing their potential of differentiating in all three germ layers. This iPSC line, carrying a pathogenic FUS variant, is a valuable tool to deeply investigate pathogenic mechanisms leading to ALS.
Published: 2021

7. Generation of an induced pluripotent stem cell line (CSS012-A (7672)) carrying the p.G376D heterozygous mutation in the TARDBP protein

Author: D'Anzi, A, Altieri, F, Perciballi, E, Ferrari, D, Torres, B, Bernardini, L, Lattante, S, Sabatelli, M, Vescovi, A, Rosati, J, D'Anzi A., Altieri F., Perciballi E., Ferrari D., Torres B., Bernardini L., Lattante S., Sabatelli M., Vescovi A. L., Rosati J., D'Anzi, A, Altieri, F, Perciballi, E, Ferrari, D, Torres, B, Bernardini, L, Lattante, S, Sabatelli, M, Vescovi, A, Rosati, J, D'Anzi A., Altieri F., Perciballi E., Ferrari D., Torres B., Bernardini L., Lattante S., Sabatelli M., Vescovi A. L., and Rosati J.
Abstract: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative condition with phenotypic and genetic heterogeneity. It is characterized by the selective vulnerability and the progressive loss of the neural population. Here, an induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of an individual carrying the p.G376D mutation in the TDP-43 protein. Fibroblasts were reprogrammed using non-integrating episomal plasmids. There were no karyotype abnormalities, and iPSCs successfully differentiated into all three germ layers. This cell line may prove useful in the study of the pathogenic mechanisms that underpin ALS syndrome.
Published: 2021

8. Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Author: Johnson, JO, Chia, R, Miller, DE, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, AE, Topp, SD, Gibbs, JR, Cookson, MR, Sabir, MS, Dalgard, CL, Troakes, C, Jones, AR, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, IP, Dobson-Stone, C, Kwok, JB, Bonkowski, ES, Palvadeau, R, Tienari, PJ, Morrison, KE, Shaw, PJ, Al-Chalabi, A, Brown, RH, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, IJ, Perlman, SJ, Glass, I, Scott, AI, Shaw, CE, Basak, AN, Landers, JE, Chiò, A, Crawford, TO, Smith, BN, Traynor, BJ, Fallini, C, Gkazi, AS, Scotter, EL, Kenna, KP, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, ten Asbroek, ALMA, McKenna-Yasek, D, McLaughlin, RL, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D’Alfonso, S, Mazzini, L, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, KL, Nicholson, GA, Leblond-Manry, C, Rouleau, GA, Hardiman, O, Veldink, JH, van den Berg, LH, Pall, H, Turner, MR, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, JD, Ratti, A, Adeleye, A, Soltis, AR, Alba, C, Viollet, C, Bacikova, D, Hupalo, DN, Sukumar, G, Pollard, HB, Wilkerson, MD, Martinez, EM, Ahmed, S, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, England, BK, Faghri, F, Feldman, E, Floeter, MK, Fratta, P, Geiger, JT, Gerhard, G, Gibson, SB, Hardy, J, Harms, MB, Heiman-Patterson, TD, Hernandez, DG, Jansson, L, Kirby, J, Kowall, NW, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering-Brown, S, Pioro, EP, Pletnikova, O, Pliner, HA, Pulst, SM, Ravits, JM, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Scholz, SW, Sendtner, M, Sidle, KC, Simmons, Z, Singleton, AB, Smith, N, Stone, DJ, Troncoso, JC, Valori, M, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Angelocola, SM, Ausiello, FP, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, TA, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, FL, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D’Errico, E, DeMarco, G, Dubbioso, R, Ferrarese, C, Ferraro, PM, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, FO, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, MG, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, MR, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson J.O., Chia R., Miller D.E., Li R., Kumaran R., Abramzon Y., Alahmady N., Renton A.E., Topp S.D., Gibbs J.R., Cookson M.R., Sabir M.S., Dalgard C.L., Troakes C., Jones A.R., Shatunov A., Iacoangeli A., Al Khleifat A., Ticozzi N., Silani V., Gellera C., Blair I.P., Dobson-Stone C., Kwok J.B., Bonkowski E.S., Palvadeau R., Tienari P.J., Morrison K.E., Shaw P.J., Al-Chalabi A., Brown R.H., Calvo A., Mora G., Al-Saif H., Gotkine M., Leigh F., Chang I.J., Perlman S.J., Glass I., Scott A.I., Shaw C.E., Basak A.N., Landers J.E., Chio A., Crawford T.O., Smith B.N., Traynor B.J., Fallini C., Gkazi A.S., Scotter E.L., Kenna K.P., Keagle P., Tiloca C., Vance C., Colombrita C., King A., Pensato V., Castellotti B., Baas F., Ten Asbroek A.L.M.A., McKenna-Yasek D., McLaughlin R.L., Polak M., Asress S., Esteban-Perez J., Stevic Z., D'Alfonso S., Mazzini L., Comi G.P., Del Bo R., Ceroni M., Gagliardi S., Querin G., Bertolin C., Van Rheenen W., Rademakers R., Van Blitterswijk M., Lauria G., Duga S., Corti S., Cereda C., Corrado L., Soraru G., Williams K.L., Nicholson G.A., Leblond-Manry C., Rouleau G.A., Hardiman O., Veldink J.H., Van Den Berg L.H., Pall H., Turner M.R., Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., Ratti A., Adeleye A., Soltis A.R., Alba C., Viollet C., Bacikova D., Hupalo D.N., Sukumar G., Pollard H.B., Wilkerson M.D., Martinez E.M., Ahmed S., Arepalli S., Baloh R.H., Bowser R., Brady C.B., Brice A., Broach J., Campbell R.H., Camu W., Cooper-Knock J., Ding J., Drepper C., Drory V.E., Dunckley T.L., Eicher J.D., England B.K., Faghri F., Feldman E., Floeter M.K., Fratta P., Geiger J.T., Gerhard G., Gibson S.B., Hardy J., Harms M.B., Heiman-Patterson T.D., Hernandez D.G., Jansson L., Kirby J., Kowall N.W., Laaksovirta H., Landeck N., Landi F., Le Ber I., Lumbroso S., Macgowan D.J.L., Maragakis N.J., Mouzat K., Murphy N.A., Myllykangas L., Nalls M.A., Orrell R.W., Ostrow L.W., Pamphlett R., Pickering-Brown S., Pioro E.P., Pletnikova O., Pliner H.A., Pulst S.M., Ravits J.M., Rivera A., Robberecht W., Rogaeva E., Rollinson S., Rothstein J.D., Scholz S.W., Sendtner M., Sidle K.C., Simmons Z., Singleton A.B., Smith N., Stone D.J., Troncoso J.C., Valori M., Van Damme P., Van Deerlin V.M., Van Den Bosch L., Zinman L., Angelocola S.M., Ausiello F.P., Barberis M., Bartolomei I., Battistini S., Bersano E., Bisogni G., Borghero G., Brunetti M., Cabona C., Canale F., Canosa A., Cantisani T.A., Capasso M., Caponnetto C., Cardinali P., Carrera P., Casale F., Colletti T., Conforti F.L., Conte A., Conti E., Corbo M., Cuccu S., Dalla Bella E., D'Errico E., Demarco G., Dubbioso R., Ferrarese C., Ferraro P.M., Filippi M., Fini N., Floris G., Fuda G., Gallone S., Gianferrari G., Giannini F., Grassano M., Greco L., Iazzolino B., Introna A., La Bella V., Lattante S., Liguori R., Logroscino G., Logullo F.O., Lunetta C., Mandich P., Mandrioli J., Manera U., Manganelli F., Marangi G., Marinou K., Marrosu M.G., Martinelli I., Messina S., Moglia C., Mosca L., Murru M.R., Origone P., Passaniti C., Petrelli C., Petrucci A., Pozzi S., Pugliatti M., Quattrini A., Ricci C., Riolo G., Riva N., Russo M., Sabatelli M., Salamone P., Salivetto M., Salvi F., Santarelli M., Sbaiz L., Sideri R., Simone I., Simonini C., Spataro R., Tanel R., Tedeschi G., Ticca A., Torriello A., Tranquilli S., Tremolizzo L., Trojsi F., Vasta R., Vacchiano V., Vita G., Volanti P., Zollino M., Zucchi E., Johnson, J. O., Chia, R., Miller, D. E., Li, R., Kumaran, R., Abramzon, Y., Alahmady, N., Renton, A. E., Topp, S. D., Gibbs, J. R., Cookson, M. R., Sabir, M. S., Dalgard, C. L., Troakes, C., Jones, A. R., Shatunov, A., Iacoangeli, A., Al Khleifat, A., Ticozzi, N., Silani, V., Gellera, C., Blair, I. P., Dobson-Stone, C., Kwok, J. B., Bonkowski, E. S., Palvadeau, R., Tienari, P. J., Morrison, K. E., Shaw, P. J., Al-Chalabi, A., Brown, R. H., Calvo, A., Mora, G., Al-Saif, H., Gotkine, M., Leigh, F., Chang, I. J., Perlman, S. J., Glass, I., Scott, A. I., Shaw, C. E., Basak, A. N., Landers, J. E., Chio, A., Crawford, T. O., Smith, B. N., Traynor, B. J., Fallini, C., Gkazi, A. S., Scotter, E. L., Kenna, K. P., Keagle, P., Tiloca, C., Vance, C., Colombrita, C., King, A., Pensato, V., Castellotti, B., Baas, F., Ten Asbroek, A. L. M. A., McKenna-Yasek, D., Mclaughlin, R. L., Polak, M., Asress, S., Esteban-Perez, J., Stevic, Z., D'Alfonso, S., Mazzini, L., Comi, G. P., Del Bo, R., Ceroni, M., Gagliardi, S., Querin, G., Bertolin, C., Van Rheenen, W., Rademakers, R., Van Blitterswijk, M., Lauria, G., Duga, S., Corti, S., Cereda, C., Corrado, L., Soraru, G., Williams, K. L., Nicholson, G. A., Leblond-Manry, C., Rouleau, G. A., Hardiman, O., Veldink, J. H., Van Den Berg, L. H., Pall, H., Turner, M. R., Talbot, K., Taroni, F., Garcia-Redondo, A., Wu, Z., Glass, J. D., Ratti, A., Adeleye, A., Soltis, A. R., Alba, C., Viollet, C., Bacikova, D., Hupalo, D. N., Sukumar, G., Pollard, H. B., Wilkerson, M. D., Martinez, E. M., Ahmed, S., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Cooper-Knock, J., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., England, B. K., Faghri, F., Feldman, E., Floeter, M. K., Fratta, P., Geiger, J. T., Gerhard, G., Gibson, S. B., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kirby, J., Kowall, N. W., Laaksovirta, H., Landeck, N., Landi, F., Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E. P., Pletnikova, O., Pliner, H. A., Pulst, S. M., Ravits, J. M., Rivera, A., Robberecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Scholz, S. W., Sendtner, M., Sidle, K. C., Simmons, Z., Singleton, A. B., Smith, N., Stone, D. J., Troncoso, J. C., Valori, M., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Angelocola, S. M., Ausiello, F. P., Barberis, M., Bartolomei, I., Battistini, S., Bersano, E., Bisogni, G., Borghero, G., Brunetti, M., Cabona, C., Canale, F., Canosa, A., Cantisani, T. A., Capasso, M., Caponnetto, C., Cardinali, P., Carrera, P., Casale, F., Colletti, T., Conforti, F. L., Conte, A., Conti, E., Corbo, M., Cuccu, S., Dalla Bella, E., D'Errico, E., Demarco, G., Dubbioso, R., Ferrarese, C., Ferraro, P. M., Filippi, M., Fini, N., Floris, G., Fuda, G., Gallone, S., Gianferrari, G., Giannini, F., Grassano, M., Greco, L., Iazzolino, B., Introna, A., La Bella, V., Lattante, S., Liguori, R., Logroscino, G., Logullo, F. O., Lunetta, C., Mandich, P., Mandrioli, J., Manera, U., Manganelli, F., Marangi, G., Marinou, K., Marrosu, M. G., Martinelli, I., Messina, S., Moglia, C., Mosca, L., Murru, M. R., Origone, P., Passaniti, C., Petrelli, C., Petrucci, A., Pozzi, S., Pugliatti, M., Quattrini, A., Ricci, C., Riolo, G., Riva, N., Russo, M., Sabatelli, M., Salamone, P., Salivetto, M., Salvi, F., Santarelli, M., Sbaiz, L., Sideri, R., Simone, I., Simonini, C., Spataro, R., Tanel, R., Tedeschi, G., Ticca, A., Torriello, A., Tranquilli, S., Tremolizzo, L., Trojsi, F., Vasta, R., Vacchiano, V., Vita, G., Volanti, P., Zollino, M., Zucchi, E., Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Palvadeau, Robin, Johnson, Janel O., Chia, Ruth, Miller, Danny E., Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E., Topp, Simon D., Gibbs, J. Raphael, Cookson, Mark R., Sabir, Marya S., Dalgard, Clifton L., Troakes, Claire, Jones, Ashley R., Shatunov, Aleksey, Lacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P., Dobson-Stone, Carol, Kwok, John B., Bonkowski, Emily S., Tienari, Pentti J., Morrison, Karen E., Shaw, Pamela J., Al-Chalabi, Ammar, Jr, Robert H. Brown, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J., Perlman, Seth J., Glass, Ian, Scott, Anna, I., Landers, John E., Chio, Adriano, Crawford, Thomas O., Smith, Bradley N., Traynor, Bryan J., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, HUS Neurocenter, Department of Neurosciences, Clinicum, Neurologian yksikkö, TRIMM - Translational Immunology Research Program, Pentti Tienari / Principal Investigator, Human Genetics, ARD - Amsterdam Reproduction and Development, ANS - Complex Trait Genetics, Johnson, Janel O, Miller, Danny E, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Jones, Ashley R, Iacoangeli, Alfredo, Blair, Ian P, Kwok, John B, Bonkowski, Emily S, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Brown, Robert H, Chang, Irene J, Perlman, Seth J, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, Mclaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesú, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexi, Broach, Jame, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, Demarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta
Subjects: Hereditary sensory neuropathy, L-serine, Mutations, Deoxysphingolipids, Accumulation, Enzyme complex, Juvenile amyotrophic lateral sclerosis, Serine C-Palmitoyltransferase, Whole Exome Sequencing, 0302 clinical medicine, Medicine, Family history, Amyotrophic lateral sclerosis, Child, Index case, Exome sequencing, Original Investigation, 0303 health sciences, Neurosciences and neurology, 3. Good health, Child, Preschool, Failure to thrive, Female, medicine.symptom, Life Sciences & Biomedicine, L-SERINE, Comments, Human, Adult, medicine.medical_specialty, Adolescent, Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease, Humans, Mutation, Young Adult, Clinical Neurology, NO, 03 medical and health sciences, DEOXYSPHINGOLIPIDS, Internal medicine, Exome Sequencing, Online First, Juvenile, Preschool, 030304 developmental biology, ACCUMULATION, Science & Technology, SPTLC1, business.industry, MUTATIONS, Research, 3112 Neurosciences, medicine.disease, HEREDITARY SENSORY NEUROPATHY, juvenile, 3111 Biomedicine, Neurology (clinical), Neurosciences & Neurology, ALS, genetic, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract: Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder., This genetic association study identifies genetic variants associated with juvenile amyotrophic lateral sclerosis., Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
Published: 2021
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9. Adult phenotype in Koolen-de Vries/KANSL1 haploinsufficiency syndrome

Author: Amenta, S., Frangella, S., Marangi, G., Lattante, S., Ricciardi, S., Doronzio, P. N., Orteschi, D., Veredice, C., Contaldo, I., Zampino, G., Gentile, M., Scarano, E., Graziano, C., Zollino, M., Amenta S., Frangella S., Marangi G. (ORCID:0000-0002-6898-8882), Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Veredice C., Contaldo I., Zampino G. (ORCID:0000-0003-3865-3253), Gentile M., Zollino M. (ORCID:0000-0003-4871-9519), Amenta, S., Frangella, S., Marangi, G., Lattante, S., Ricciardi, S., Doronzio, P. N., Orteschi, D., Veredice, C., Contaldo, I., Zampino, G., Gentile, M., Scarano, E., Graziano, C., Zollino, M., Amenta S., Frangella S., Marangi G. (ORCID:0000-0002-6898-8882), Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Veredice C., Contaldo I., Zampino G. (ORCID:0000-0003-3865-3253), Gentile M., and Zollino M. (ORCID:0000-0003-4871-9519)
Abstract: Background: Koolen-de Vries syndrome (KdVS) is a multisystem neurodevelopmental disorder caused by 17q21.31 deletions or mutations in KANSL1. It was mainly described in children. Methods: A retrospective study on 9 subjects aged 19-45 years and revision of 18 literature patients, with the purpose to get insights into the phenotypic evolution with time, and into the clinical manifestations in adulthood. Results: Seven patients had a 17q21.31 deletion and two a point mutation in KANSL1. All had intellectual disability, which was mild in five (56%) and moderate in four (44%). Epilepsy was diagnosed in four subjects (44%), with onset from 1 to 7 years and full remission before 9 years in 3/4 patients. Scoliosis affected seven individuals (77.7%) and it was substantially stable with age in 5/7 patients, allowing for simple daily activities. Two subjects had severely progressive scoliosis, which was surgically corrected. Overweight or true obesity did occur after puberty in six patients (67%). Behaviour abnormalities were recorded in six patients (67%). The facial phenotype slightly evolved with time to include thick eyebrows, elongated nose and pronounced pointed chin. Despite behaviour abnormalities, happy disposition and sociable attitudes were common. Half of patients had fluent language and were good at writing and reading. Rich language, although limited to single words or short sentences, and very limited or absent skills in writing and reading were observed in the remaining patients. Autonomy in daily activities and personal care was usually limited. Conclusions: Distinctive features in adult KdVS subjects include intellectual disability, overweight/obesity, behaviour abnormalities with preserved social interest, ability in language, slight worsening of the facial phenotype and no seizures.
Published: 2020

10. Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Author: Perciballi, E, Bovio, F, Rosati, J, Arrigoni, F, D'Anzi, A, Lattante, S, Gelati, M, De Marchi, F, Lombardi, I, Ruotolo, G, Forcella, M, Mazzini, L, D'Alfonso, S, Corrado, L, Sabatelli, M, Conte, A, De Gioia, L, Martino, S, Vescovi, A, Fusi, P, Ferrari, D, Perciballi, Elisa, Bovio, Federica, Rosati, Jessica, Arrigoni, Federica, D'Anzi, Angela, Lattante, Serena, Gelati, Maurizio, De Marchi, Fabiola, Lombardi, Ivan, Ruotolo, Giorgia, Forcella, Matilde, Mazzini, Letizia, D'Alfonso, Sandra, Corrado, Lucia, Sabatelli, Mario, Conte, Amelia, De Gioia, Luca, Martino, Sabata, Vescovi, Angelo Luigi, Fusi, Paola, Ferrari, Daniela, Perciballi, E, Bovio, F, Rosati, J, Arrigoni, F, D'Anzi, A, Lattante, S, Gelati, M, De Marchi, F, Lombardi, I, Ruotolo, G, Forcella, M, Mazzini, L, D'Alfonso, S, Corrado, L, Sabatelli, M, Conte, A, De Gioia, L, Martino, S, Vescovi, A, Fusi, P, Ferrari, D, Perciballi, Elisa, Bovio, Federica, Rosati, Jessica, Arrigoni, Federica, D'Anzi, Angela, Lattante, Serena, Gelati, Maurizio, De Marchi, Fabiola, Lombardi, Ivan, Ruotolo, Giorgia, Forcella, Matilde, Mazzini, Letizia, D'Alfonso, Sandra, Corrado, Lucia, Sabatelli, Mario, Conte, Amelia, De Gioia, Luca, Martino, Sabata, Vescovi, Angelo Luigi, Fusi, Paola, and Ferrari, Daniela
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism.
Published: 2022

11. Generation of an induced pluripotent stem cell line (UCSCi002-A) from a patient with a variant in TARDBP gene associated with familial amyotrophic lateral sclerosis and frontotemporal dementia

Author: Martello, Francesco, Lattante, Serena, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Orteschi, D., Luigetti, Marco, Marrucci, M. A., Zollino, Marcella, Sabatelli, Mario, Marangi, Giuseppe, Martello F., Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Luigetti M. (ORCID:0000-0001-7539-505X), Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), Marangi G. (ORCID:0000-0002-6898-8882), Martello, Francesco, Lattante, Serena, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Orteschi, D., Luigetti, Marco, Marrucci, M. A., Zollino, Marcella, Sabatelli, Mario, Marangi, Giuseppe, Martello F., Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Luigetti M. (ORCID:0000-0001-7539-505X), Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), and Marangi G. (ORCID:0000-0002-6898-8882)
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively affects motor neurons. In 20% of cases, ALS appears in comorbidity with frontotemporal dementia (FTD). We generated patient-derived-induced Pluripotent Stem Cells (iPSCs), from an ALS/FTD patient. The patient had a familial form of the disease and a missense variant in TARDBP gene. We used an established protocol based on Sendai virus to reprogram fibroblasts. We confirmed the stemness and the pluripotency of the iPSC clones, thus generating embryoid bodies. We believe that the iPSC line carrying a TARDBP mutation could be a valuable tool to investigate TDP-43 proteinopathy linked to ALS.
Published: 2022

12. Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376D TARDBP mutation

Author: Romano, R., De Luca, M., Del Fiore, V. S., Pecoraro, M., Lattante, Serena, Sabatelli, Mario, La Bella, V., Bucci, C., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Romano, R., De Luca, M., Del Fiore, V. S., Pecoraro, M., Lattante, Serena, Sabatelli, Mario, La Bella, V., Bucci, C., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons. There is no treatment for this disease that affects the ability to move, eat, speak and finally breathe, causing death. In an Italian family, a heterozygous pathogenic missense variant has been previously discovered in Exon 6 of the gene TARDBP encoding the TAR DNA-binding protein 43 protein. Here, we developed a potential therapeutic tool based on allele-specific small interfering RNAs for familial amyotrophic lateral sclerosis with the heterozygous missense mutation c.1127G > A. We designed a small interfering RNA that was able to diminish specifically the expression of the exogenous Green Fluorescent Protein (TAR DNA-binding protein 43(G376D) mutant protein) in HEK-293T cells but not that of the Green Fluorescent Protein (TAR DNA-binding protein 43 wild-type). Similarly, this small interfering RNA silenced the mutated allele in fibroblasts derived from patients with amyotrophic lateral sclerosis but did not silence the wild-type gene in control fibroblasts. In addition, we established that silencing the mutated allele was able to strongly reduce the pathological cellular phenotypes induced by TAR DNA-binding protein 43(G376D) expression, such as the presence of cytoplasmic aggregates. Thus, we have identified a small interfering RNA that could be used to silence specifically the mutated allele to try a targeted therapy for patients carrying the p.G376D TAR DNA-binding protein 43 mutation.
Published: 2022

13. Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Author: Perciballi, E., Bovio, F., Rosati, J., Arrigoni, F., D'Anzi, A., Lattante, Serena, Gelati, M., De Marchi, F., Lombardi, I., Ruotolo, G., Forcella, M., Mazzini, L., D'Alfonso, S., Corrado, L., Sabatelli, Mario, Conte, A., De Gioia, L., Martino, S., Vescovi, A. L., Fusi, P., Ferrari, D., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Perciballi, E., Bovio, F., Rosati, J., Arrigoni, F., D'Anzi, A., Lattante, Serena, Gelati, M., De Marchi, F., Lombardi, I., Ruotolo, G., Forcella, M., Mazzini, L., D'Alfonso, S., Corrado, L., Sabatelli, Mario, Conte, A., De Gioia, L., Martino, S., Vescovi, A. L., Fusi, P., Ferrari, D., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism.
Published: 2022

14. FUS mutations dominate TBK1 mutations in FUS/TBK1 double-mutant ALS/FTD pedigrees

Author: Brenner, D., Muller, K., Lattante, Serena, Yilmaz, R., Knehr, A., Freischmidt, A., Ludolph, A. C., Andersen, P. M., Weishaupt, J. H., Lattante S. (ORCID:0000-0003-2891-0340), Brenner, D., Muller, K., Lattante, Serena, Yilmaz, R., Knehr, A., Freischmidt, A., Ludolph, A. C., Andersen, P. M., Weishaupt, J. H., and Lattante S. (ORCID:0000-0003-2891-0340)
Abstract: Mutations in FUS and TBK1 often cause aggressive early-onset amyotrophic lateral sclerosis (ALS) or a late-onset ALS and/or frontotemporal dementia (FTD) phenotype, respectively. Co-occurrence of mutations in two or more Mendelian ALS/FTD genes has been repeatedly reported. However, little is known how two pathogenic ALS/FTD mutations in the same patient interact to shape the final phenotype. We screened 28 ALS patients with a known FUS mutation by whole-exome sequencing and targeted evaluation for mutations in other known ALS genes followed by genotype–phenotype correlation analysis of FUS/TBK1 double-mutant patients. We report on new and summarize previously published FUS and TBK1 double-mutant ALS/FTD patients and their families. We found that, within a family, mutations in FUS cause ALS while TBK1 single mutations are observed in FTD patients. FUS/TBK1 double mutations manifested as ALS and without a manifest difference regarding age at onset and disease duration when compared to FUS single-mutant individuals. In conclusion, TBK1 and FUS variants do not seem to interact in a simple additive way. Rather, the phenotype of FUS/TBK1 double-mutant patients appears to be dominated by the FUS mutation.
Published: 2022

15. MAPLE-deposited PFO films: influence of the laser fluence and repetition rate on the film emission and morphology

Author: Caricato, A. P., Anni, M., Cesaria, M., Lattante, S., Leggieri, G., Leo, C., Martino, M., Perulli, A., and Resta, V.
Published: 2015
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16. D11Y SOD1 mutation and benign ALS: A consistent genotype-phenotype correlation

Author: Del Grande, A., Conte, A., Lattante, S., Luigetti, M., Marangi, G., Zollino, M., Madia, F., Bisogni, G., and Sabatelli, M.
Published: 2011
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17. Clinical Heterogeneity of ALS-Implications for Models and Therapeutic Development

Author: Christopher A. Shaw, Jessica R. Morrice, Lattante, Serena, Sabatelli, Mario, Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Christopher A. Shaw, Jessica R. Morrice, Lattante, Serena, Sabatelli, Mario, Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder affecting both upper and lower motor neurons. Based on age at onset, site of onset, disease duration, and relative predominance of upper or lower motor neuron signs, clinical manifestations of ALS are very heterogeneous, and different clinical subtypes may be delineated. Although ALS has long been considered a paradigm of pure motor neuron disorder, it has recently been linked to other neurological diseases. Clinical, genetic, and/or neuropathological overlap exists with frontotemporal dementia, distal myopathies, psychiatric disorders, and extrapyramidal syndromes. This clinical heterogeneity can depend on the pleiotropy of ALS-associated genes and by the oligogenic model of disease mechanism. A number of animal models have been created, each of them recapitulating some clinical and neuropathological features of patients. More recently, induced pluripotent stem cells have been used, directly derived from affected patients with different genetic mutations. The combination of animal and cellular models represents an advanced tool that can help to functionally characterize the pathogenetic mechanisms underlying the disease and specifically find efficient and personalized drugs to treat ALS patients.
Published: 2021

18. SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration

Author: Barbier, M., Camuzat, A., Hachimi, K. E., Guegan, J., Rinaldi, D., Lattante, Serena, Houot, M., Sanchez-Valle, R., Sabatelli, Mario, Antonell, A., Molina-Porcel, L., Clot, F., Couratier, P., Van Der Ende, E., Van Der Zee, J., Manzoni, C., Camu, W., Cazeneuve, C., Sellal, F., Didic, M., Golfier, V., Pasquier, F., Duyckaerts, C., Rossi, G., Bruni, A. C., Alvarez, V., Gomez-Tortosa, E., De Mendonca, A., Graff, C., Masellis, M., Nacmias, B., Oumoussa, B. M., Jornea, L., Forlani, S., Van Deerlin, V., Rohrer, J. D., Gelpi, E., Rademakers, R., Van Swieten, J., Le Guern, E., Van Broeckhoven, C., Ferrari, R., Genin, E., Brice, A., Le Ber, I., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Barbier, M., Camuzat, A., Hachimi, K. E., Guegan, J., Rinaldi, D., Lattante, Serena, Houot, M., Sanchez-Valle, R., Sabatelli, Mario, Antonell, A., Molina-Porcel, L., Clot, F., Couratier, P., Van Der Ende, E., Van Der Zee, J., Manzoni, C., Camu, W., Cazeneuve, C., Sellal, F., Didic, M., Golfier, V., Pasquier, F., Duyckaerts, C., Rossi, G., Bruni, A. C., Alvarez, V., Gomez-Tortosa, E., De Mendonca, A., Graff, C., Masellis, M., Nacmias, B., Oumoussa, B. M., Jornea, L., Forlani, S., Van Deerlin, V., Rohrer, J. D., Gelpi, E., Rademakers, R., Van Swieten, J., Le Guern, E., Van Broeckhoven, C., Ferrari, R., Genin, E., Brice, A., Le Ber, I., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10-5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier g
Published: 2021

19. Generation of an induced pluripotent stem cell line (CSS012-A (7672)) carrying the p.G376D heterozygous mutation in the TARDBP protein

Author: D'Anzi, A., Altieri, F., Perciballi, E., Ferrari, D., Torres, B., Bernardini, L., Lattante, Serena, Sabatelli, Mario, Vescovi, A. L., Rosati, J., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), D'Anzi, A., Altieri, F., Perciballi, E., Ferrari, D., Torres, B., Bernardini, L., Lattante, Serena, Sabatelli, Mario, Vescovi, A. L., Rosati, J., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative condition with phenotypic and genetic heterogeneity. It is characterized by the selective vulnerability and the progressive loss of the neural population. Here, an induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of an individual carrying the p.G376D mutation in the TDP-43 protein. Fibroblasts were reprogrammed using non-integrating episomal plasmids. There were no karyotype abnormalities, and iPSCs successfully differentiated into all three germ layers. This cell line may prove useful in the study of the pathogenic mechanisms that underpin ALS syndrome.
Published: 2021

20. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Author: Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, Zucchi, Elisabetta, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta
Abstract: Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, setting, and participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main outcomes and measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis
Published: 2021

21. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B. J., Nalls, M. A., Keagle, P., Rivera, A. M., van Rheenen, W., Murphy, N. A., van Vugt, J. J. F. A., Geiger, J. T., Van der Spek, R. A., Pliner, H. A., Shankaracharya, Smith, B. N., Marangi, G., Topp, S. D., Abramzon, Y., Gkazi, A. S., Eicher, J. D., Kenna, A., Logullo, F. O., Simone, I. L., Logroscino, G., Salvi, F., Bartolomei, I., Borghero, G., Murru, M. R., Costantino, E., Pani, C., Puddu, R., Caredda, C., Piras, V., Tranquilli, S., Cuccu, S., Corongiu, D., Melis, M., Milia, A., Marrosu, F., Marrosu, M. G., Floris, G., Cannas, A., Capasso, Monica, Caponnetto, C., Mancardi, G., Origone, P., Mandich, P., Conforti, F. L., Cavallaro, S., Mora, G., Marinou, K., Sideri, R., Penco, S., Mosca, L., Lunetta, C., Pinter, G. L., Corbo, M., Riva, N., Carrera, P., Volanti, P., Mandrioli, J., Fini, N., Fasano, A., Tremolizzo, L., Arosio, A., Ferrarese, C., Trojsi, F., Tedeschi, G., Monsurro, M. R., Piccirillo, G., Femiano, C., Ticca, A., Ortu, E., La Bella, V., Spataro, R., Colletti, T., Sabatelli, M., Zollino, M., Conte, A., Luigetti, M., Lattante, S., Santarelli, M., Petrucci, A., Pugliatti, M., Pirisi, A., Parish, L. D., Occhineri, P., Giannini, F., Battistini, S., Ricci, C., Benigni, M., Cau, T. B., Loi, D., Calvo, A., Moglia, C., Brunetti, M., Barberis, M., Restagno, G., Casale, F., Marrali, G., Fuda, G., Ossola, I., Cammarosano, S., Canosa, A., Ilardi, A., Manera, U., Grassano, M., Tanel, R., Pisano, F., Mazzini, L., Messina, S., D'Alfonso, S., Corrado, L., Ferrucci, L., Harms, M. B., Goldstein, D. B., Shneider, N. A., Goutman, S. A., Simmons, Z., Miller, T. M., Chandran, S., Pal, S., Manousakis, G., Appel, S. H., Simpson, E., Wang, L., Baloh, R. H., Gibson, S. B., Bedlack, R., Lacomis, D., Sareen, D., Sherman, A., Bruijn, L., Penny, M., Moreno, C. D. A. M., Kamalakaran, S., Allen, A. S., Boone, B. E., Brown, R. H., Carulli, J. P., Chesi, A., Chung, W. K., Cirulli, E. T., Cooper, G. M., Couthouis, J., Day-Williams, A. G., Dion, P. A., Gitler, A. D., Glass, J. D., Han, Y., Harris, T., Hayes, S. D., Jones, A. L., Keebler, J., Krueger, B. J., Lasseigne, B. N., Levy, S. E., Lu, Y. -F., Maniatis, T., McKenna-Yasek, D., Myers, R. M., Petrovski, S., Pulst, S. M., Raphael, A. R., Ravits, J. M., Ren, Z., Rouleau, G. A., Sapp, P. C., Sims, K. B., Staropoli, J. F., Waite, L. L., Wang, Q., Wimbish, J. R., Xin, W. W., Phatnani, H., Kwan, J., Broach, J., Arcila-Londono, X., Lee, E. B., Van Deerlin, V. M., Fraenkel, E., Ostrow, L. W., Baas, F., Zaitlen, N., Berry, J. D., Malaspina, A., Fratta, P., Cox, G. A., Thompson, L. M., Finkbeiner, S., Dardiotis, E., Hornstein, E., MacGowan, D. J. L., Heiman-Patterson, T., Hammell, M. G., Patsopoulos, N. A., Dubnau, J., Nath, A., Musunuri, R. L., Evani, U. S., Abhyankar, A., Zody, M. C., Kaye, J., Wyman, S. K., LeNail, A., Lima, L., Rothstein, J. D., Svendsen, C. N., Van Eyk, J. E., Maragakis, N. J., Kolb, S. J., Cudkowicz, M., Baxi, E., Benatar, M., Taylor, J. P., Wu, G., Rampersaud, E., Wuu, J., Rademakers, R., Zuchner, S., Schule, R., McCauley, J., Hussain, S., Cooley, A., Wallace, M., Clayman, C., Barohn, R., Statland, J., Swenson, A., Jackson, C., Trivedi, J., Khan, S., Katz, J., Jenkins, L., Burns, T., Gwathmey, K., Caress, J., McMillan, C., Elman, L., Pioro, E. P., Heckmann, J., So, Y., Walk, D., Maiser, S., Zhang, J., Silani, V., Gellera, C., Ratti, A., Taroni, F., Lauria, G., Verde, F., Fogh, I., Tiloca, C., Comi, G. P., Soraru, G., Cereda, C., De Marchi, F., Corti, S., Ceroni, M., Siciliano, G., Filosto, M., Inghilleri, M., Peverelli, S., Colombrita, C., Poletti, B., Maderna, L., Del Bo, R., Gagliardi, S., Querin, G., Bertolin, C., Pensato, V., Castellotti, B., Camu, W., Mouzat, K., Lumbroso, S., Corcia, P., Meininger, V., Besson, G., Lagrange, E., Clavelou, P., Guy, N., Couratier, P., Vourch, P., Danel, V., Bernard, E., Lemasson, G., Laaksovirta, H., Myllykangas, L., Jansson, L., Valori, M., Ealing, J., Hamdalla, H., Rollinson, S., Pickering-Brown, S., Orrell, R. W., Sidle, K. C., Hardy, J., Singleton, A. B., Johnson, J. O., Arepalli, S., Polak, M., Asress, S., Al-Sarraj, S., King, A., Troakes, C., Vance, C., de Belleroche, J., ten Asbroek, A. L. M. A., Munoz-Blanco, J. L., Hernandez, D. G., Ding, J., Gibbs, J. R., Scholz, S. W., Floeter, M. K., Campbell, R. H., Landi, F., Bowser, R., Kirby, J., Pamphlett, R., Gerhard, G., Dunckley, T. L., Brady, C. B., Kowall, N. W., Troncoso, J. C., Le Ber, I., Heiman-Patterson, T. D., Kamel, F., Van Den Bosch, L., Strom, T. M., Meitinger, T., Shatunov, A., Van Eijk, K. R., de Carvalho, M., Kooyman, M., Middelkoop, B., Moisse, M., McLaughlin, R. L., Van Es, M. A., Weber, M., Boylan, K. B., Van Blitterswijk, M., Morrison, K. E., Basak, A. N., Mora, J. S., Drory, V. E., Shaw, P. J., Turner, M. R., Talbot, K., Hardiman, O., Williams, K. L., Fifita, J. A., Nicholson, G. A., Blair, I. P., Esteban-Perez, J., Garcia-Redondo, A., Al-Chalabi, A., Al Kheifat, A., Andersen, P. M., Chio, A., Cooper-Knock, J., Dekker, A., Redondo, A. G., Gotkine, M., Hide, W., Iacoangeli, A., Kiernan, M., Landers, J. E., Mill, J., Neto, M. M., Pardina, J. M., Newhouse, S., Pinto, S., Pulit, S., Robberecht, W., Shaw, C., Sproviero, W., Tazelaar, G., Van Damme, P., van den Berg, L. H., van Vugt, J., Veldink, J. H., Zatz, M., Bauer, D. C., Twine, N. A., Rogaeva, E., Zinman, L., Brice, A., Feldman, E. L., Ludolph, A. C., Weishaupt, J. H., Trojanowski, J. Q., Stone, D. J., Tienari, P., Shaw, C. E., Traynor, B. J., Marangi G. (ORCID:0000-0002-6898-8882), Logroscino G. (ORCID:0000-0003-1301-5343), Mosca L. (ORCID:0000-0003-4641-0841), Fasano A., Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Conte A., Luigetti M. (ORCID:0000-0001-7539-505X), Lattante S. (ORCID:0000-0003-2891-0340), D'Alfonso S., Siciliano G., Valori M., Landi F. (ORCID:0000-0002-3472-1389), Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B. J., Nalls, M. A., Keagle, P., Rivera, A. M., van Rheenen, W., Murphy, N. A., van Vugt, J. J. F. A., Geiger, J. T., Van der Spek, R. A., Pliner, H. A., Shankaracharya, Smith, B. N., Marangi, G., Topp, S. D., Abramzon, Y., Gkazi, A. S., Eicher, J. D., Kenna, A., Logullo, F. O., Simone, I. L., Logroscino, G., Salvi, F., Bartolomei, I., Borghero, G., Murru, M. R., Costantino, E., Pani, C., Puddu, R., Caredda, C., Piras, V., Tranquilli, S., Cuccu, S., Corongiu, D., Melis, M., Milia, A., Marrosu, F., Marrosu, M. G., Floris, G., Cannas, A., Capasso, Monica, Caponnetto, C., Mancardi, G., Origone, P., Mandich, P., Conforti, F. L., Cavallaro, S., Mora, G., Marinou, K., Sideri, R., Penco, S., Mosca, L., Lunetta, C., Pinter, G. L., Corbo, M., Riva, N., Carrera, P., Volanti, P., Mandrioli, J., Fini, N., Fasano, A., Tremolizzo, L., Arosio, A., Ferrarese, C., Trojsi, F., Tedeschi, G., Monsurro, M. R., Piccirillo, G., Femiano, C., Ticca, A., Ortu, E., La Bella, V., Spataro, R., Colletti, T., Sabatelli, M., Zollino, M., Conte, A., Luigetti, M., Lattante, S., Santarelli, M., Petrucci, A., Pugliatti, M., Pirisi, A., Parish, L. D., Occhineri, P., Giannini, F., Battistini, S., Ricci, C., Benigni, M., Cau, T. B., Loi, D., Calvo, A., Moglia, C., Brunetti, M., Barberis, M., Restagno, G., Casale, F., Marrali, G., Fuda, G., Ossola, I., Cammarosano, S., Canosa, A., Ilardi, A., Manera, U., Grassano, M., Tanel, R., Pisano, F., Mazzini, L., Messina, S., D'Alfonso, S., Corrado, L., Ferrucci, L., Harms, M. B., Goldstein, D. B., Shneider, N. A., Goutman, S. A., Simmons, Z., Miller, T. M., Chandran, S., Pal, S., Manousakis, G., Appel, S. H., Simpson, E., Wang, L., Baloh, R. H., Gibson, S. B., Bedlack, R., Lacomis, D., Sareen, D., Sherman, A., Bruijn, L., Penny, M., Moreno, C. D. A. M., Kamalakaran, S., Allen, A. S., Boone, B. E., Brown, R. H., Carulli, J. P., Chesi, A., Chung, W. K., Cirulli, E. T., Cooper, G. M., Couthouis, J., Day-Williams, A. G., Dion, P. A., Gitler, A. D., Glass, J. D., Han, Y., Harris, T., Hayes, S. D., Jones, A. L., Keebler, J., Krueger, B. J., Lasseigne, B. N., Levy, S. E., Lu, Y. -F., Maniatis, T., McKenna-Yasek, D., Myers, R. M., Petrovski, S., Pulst, S. M., Raphael, A. R., Ravits, J. M., Ren, Z., Rouleau, G. A., Sapp, P. C., Sims, K. B., Staropoli, J. F., Waite, L. L., Wang, Q., Wimbish, J. R., Xin, W. W., Phatnani, H., Kwan, J., Broach, J., Arcila-Londono, X., Lee, E. B., Van Deerlin, V. M., Fraenkel, E., Ostrow, L. W., Baas, F., Zaitlen, N., Berry, J. D., Malaspina, A., Fratta, P., Cox, G. A., Thompson, L. M., Finkbeiner, S., Dardiotis, E., Hornstein, E., MacGowan, D. J. L., Heiman-Patterson, T., Hammell, M. G., Patsopoulos, N. A., Dubnau, J., Nath, A., Musunuri, R. L., Evani, U. S., Abhyankar, A., Zody, M. C., Kaye, J., Wyman, S. K., LeNail, A., Lima, L., Rothstein, J. D., Svendsen, C. N., Van Eyk, J. E., Maragakis, N. J., Kolb, S. J., Cudkowicz, M., Baxi, E., Benatar, M., Taylor, J. P., Wu, G., Rampersaud, E., Wuu, J., Rademakers, R., Zuchner, S., Schule, R., McCauley, J., Hussain, S., Cooley, A., Wallace, M., Clayman, C., Barohn, R., Statland, J., Swenson, A., Jackson, C., Trivedi, J., Khan, S., Katz, J., Jenkins, L., Burns, T., Gwathmey, K., Caress, J., McMillan, C., Elman, L., Pioro, E. P., Heckmann, J., So, Y., Walk, D., Maiser, S., Zhang, J., Silani, V., Gellera, C., Ratti, A., Taroni, F., Lauria, G., Verde, F., Fogh, I., Tiloca, C., Comi, G. P., Soraru, G., Cereda, C., De Marchi, F., Corti, S., Ceroni, M., Siciliano, G., Filosto, M., Inghilleri, M., Peverelli, S., Colombrita, C., Poletti, B., Maderna, L., Del Bo, R., Gagliardi, S., Querin, G., Bertolin, C., Pensato, V., Castellotti, B., Camu, W., Mouzat, K., Lumbroso, S., Corcia, P., Meininger, V., Besson, G., Lagrange, E., Clavelou, P., Guy, N., Couratier, P., Vourch, P., Danel, V., Bernard, E., Lemasson, G., Laaksovirta, H., Myllykangas, L., Jansson, L., Valori, M., Ealing, J., Hamdalla, H., Rollinson, S., Pickering-Brown, S., Orrell, R. W., Sidle, K. C., Hardy, J., Singleton, A. B., Johnson, J. O., Arepalli, S., Polak, M., Asress, S., Al-Sarraj, S., King, A., Troakes, C., Vance, C., de Belleroche, J., ten Asbroek, A. L. M. A., Munoz-Blanco, J. L., Hernandez, D. G., Ding, J., Gibbs, J. R., Scholz, S. W., Floeter, M. K., Campbell, R. H., Landi, F., Bowser, R., Kirby, J., Pamphlett, R., Gerhard, G., Dunckley, T. L., Brady, C. B., Kowall, N. W., Troncoso, J. C., Le Ber, I., Heiman-Patterson, T. D., Kamel, F., Van Den Bosch, L., Strom, T. M., Meitinger, T., Shatunov, A., Van Eijk, K. R., de Carvalho, M., Kooyman, M., Middelkoop, B., Moisse, M., McLaughlin, R. L., Van Es, M. A., Weber, M., Boylan, K. B., Van Blitterswijk, M., Morrison, K. E., Basak, A. N., Mora, J. S., Drory, V. E., Shaw, P. J., Turner, M. R., Talbot, K., Hardiman, O., Williams, K. L., Fifita, J. A., Nicholson, G. A., Blair, I. P., Esteban-Perez, J., Garcia-Redondo, A., Al-Chalabi, A., Al Kheifat, A., Andersen, P. M., Chio, A., Cooper-Knock, J., Dekker, A., Redondo, A. G., Gotkine, M., Hide, W., Iacoangeli, A., Kiernan, M., Landers, J. E., Mill, J., Neto, M. M., Pardina, J. M., Newhouse, S., Pinto, S., Pulit, S., Robberecht, W., Shaw, C., Sproviero, W., Tazelaar, G., Van Damme, P., van den Berg, L. H., van Vugt, J., Veldink, J. H., Zatz, M., Bauer, D. C., Twine, N. A., Rogaeva, E., Zinman, L., Brice, A., Feldman, E. L., Ludolph, A. C., Weishaupt, J. H., Trojanowski, J. Q., Stone, D. J., Tienari, P., Shaw, C. E., Traynor, B. J., Marangi G. (ORCID:0000-0002-6898-8882), Logroscino G. (ORCID:0000-0003-1301-5343), Mosca L. (ORCID:0000-0003-4641-0841), Fasano A., Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Conte A., Luigetti M. (ORCID:0000-0001-7539-505X), Lattante S. (ORCID:0000-0003-2891-0340), D'Alfonso S., Siciliano G., Valori M., and Landi F. (ORCID:0000-0002-3472-1389)
Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

22. High-throughput genetic testing in ALS: The challenging path of variant classification considering the acmg guidelines

Author: Lattante, Serena, Marangi, Giuseppe, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Zollino, Marcella, Sabatelli, Mario, Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Doronzio P. N., Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), Lattante, Serena, Marangi, Giuseppe, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Zollino, Marcella, Sabatelli, Mario, Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Doronzio P. N., Zollino M. (ORCID:0000-0003-4871-9519), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: The development of high-throughput sequencing technologies and screening of big patient cohorts with familial and sporadic amyotrophic lateral sclerosis (ALS) led to the identification of a significant number of genetic variants, which are sometimes difficult to interpret. The American College of Medical Genetics and Genomics (ACMG) provided guidelines to help molecular geneticists and pathologists to interpret variants found in laboratory testing. We assessed the application of the ACMG criteria to ALS-related variants, combining data from literature with our experience. We analyzed a cohort of 498 ALS patients using massive parallel sequencing of ALS-associated genes and identified 280 variants with a minor allele frequency < 1%. Examining all variants using the ACMG criteria, thus considering the type of variant, inheritance, familial segregation, and possible functional studies, we classified 20 variants as “pathogenic”. In conclusion, ALS’s genetic complexity, such as oligogenic inheritance, presence of genes acting as risk factors, and reduced penetrance, needs to be considered when interpreting variants. The goal of this work is to provide helpful suggestions to geneticists and clinicians dealing with ALS.
Published: 2020

23. Fabrication of disordered photonic crystal structures for organic random lasing devices

Author: Qualtieri, A., Stomeo, T., Lattante, S., Anni, M., Martiradonna, L., and De Vittorio, M.
Published: 2007
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24. Optical properties of N-succinimidyl bithiophene and the effects of the binding to biomolecules: Comparison between coupled-cluster and time-dependent density functional theory calculations and experiments

Author: Fabiano, E., Sala, F. Della, Barbarella, G., Lattante, S., Anni, M., Gigli, G., Sotgiu, G., Hattig, C., and Cingolani, R.
Subjects: Density functionals -- Usage, Photoluminescence -- Analysis, Thiophene -- Chemical properties, Charge transfer -- Analysis, Chemicals, plastics and rubber industries
Abstract: A joint theoretical-experimental study on the optical properties of 5-N-succinimidyl-2.2 -bithiophene (NS-2T), a prototype system for a new class of biomarkers was conducted, and time-dependent density functional theory (TD-DFT) and approximate coupled-cluster single and doubles (CC2) calculations were performed in the ground and excited states. Results showed that CC2 and TD-DFT can very well describe the absorption and photoluminescence energies of the three systems, but the presence of several charge-transfer transitions in the TD-DFT spectrum of NS-2T required the use of a correlated method to validate the TD-DFT results.
Published: 2006

25. Optical gain in fluorenyl-thiophene co-oligomer thin films

Author: Lattante, S., Anni, M., Salerno, M., Lagonigro, L., Cingolani, R., Gigli, G., Pasini, M., Destri, S., and Porzio, W.
Published: 2006
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26. SOD1 p.D12Y variant is associated with amyotrophic lateral sclerosis/distal myopathy spectrum

Author: Tasca, G., primary, Lattante, S., additional, Marangi, G., additional, Conte, A., additional, Bernardo, D., additional, Bisogni, G., additional, Mandich, P., additional, Zollino, M., additional, Ragozzino, E., additional, Udd, B., additional, and Sabatelli, M., additional
Published: 2020
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27. COntribution of S100A4-regulated pathways to inflammation in ALS models

Author: Apolloni, S, Serrano, A, Rossi, S, Mammarella, E, Milani, M, Lattante, S, Sabatelli, M, Andjus, P, Michetti, F, Carrì, M, Cozzolino, M, D'Ambrosi, N, and N
Subjects: Settore BIO/10
Published: 2019

28. The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis

Author: Serrano, A, Apolloni, S, Rossi, S, Lattante, S, Sabatelli, M, Peric, M, Andjus, P, Michetti, F, Carrì, Mt, Cozzolino, M, and D'Ambrosi, N
Subjects: Adult, Male, Blotting, Western, microglia, Real-Time Polymerase Chain Reaction, Article, NF-κB, neuroinflammation, Mice, Superoxide Dismutase-1, Phagocytosis, ALS, S100A4, astrocytes, fibroblasts, mTOR, neurodegeneration, niclosamide, Cell Movement, Settore BIO/13 - BIOLOGIA APPLICATA, Animals, Humans, S100 Calcium-Binding Protein A4, Settore BIO/10, lcsh:QH301-705.5, Cells, Cultured, TOR Serine-Threonine Kinases, Amyotrophic Lateral Sclerosis, NF-kappa B, Middle Aged, lcsh:Biology (General), Microscopy, Fluorescence, Electrophoresis, Polyacrylamide Gel, Female
Abstract: S100A4, belonging to a large multifunctional S100 protein family, is a Ca2+-binding protein with a significant role in stimulating the motility of cancer and immune cells, as well as in promoting pro-inflammatory properties in different cell types. In the CNS, there is limited information concerning S100A4 presence and function. In this study, we analyzed the expression of S100A4 and the effect of the S100A4 transcriptional inhibitor niclosamide in murine activated primary microglia. We found that S100A4 was strongly up-regulated in reactive microglia and that niclosamide prevented NADPH oxidase 2, mTOR (mammalian target of rapamycin), and NF-&kappa, B (nuclear factor-kappa B) increase, cytoskeletal rearrangements, migration, and phagocytosis. Furthermore, we found that S100A4 was significantly up-regulated in astrocytes and microglia in the spinal cord of a transgenic rat SOD1-G93A model of amyotrophic lateral sclerosis. Finally, we demonstrated the increased expression of S100A4 also in fibroblasts derived from amyotrophic lateral sclerosis (ALS) patients carrying SOD1 pathogenic variants. These results ascribe S100A4 as a marker of microglial reactivity, suggesting the contribution of S100A4-regulated pathways to neuroinflammation, and identify niclosamide as a possible drug in the control and attenuation of reactive phenotypes of microglia, thus opening the way to further investigation for a new application in neurodegenerative conditions.
Published: 2019
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29. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Author: Bandres‐Ciga, S, Noyce, AJ, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Arosio, A, Barberis, M, Bartolomei, I, Battistini, S, Benigni, M, Borghero, G, Brunetti, M, Cammarosano, S, Cannas, A, Canosa, A, Capasso, M, Caponnetto, C, Caredda, C, Carrera, P, Casale, F, Cavallaro, S, Chiò, A, Colletti, T, Conforti, FL, Conte, A, Corrado, L, Costantino, E, D'Alfonso, S, Fasano, A, Femiano, C, Ferrarese, C, Fini, N, Floris, G, Fuda, G, Giannini, F, Grassano, M, Ilardi, A, La Bella, V, Lattante, S, Logroscino, G, Logullo, FO, Loi, D, Lunetta, C, Mancardi, G, Mandich, P, Mandrioli, J, Manera, U, Marangi, G, Marinou, K, Marrali, G, Marrosu, MG, Mazzini, L, Melis, M, Messina, S, Moglia, C, Monsurro, MR, Mosca, L, Occhineri, P, Origone, P, Pani, C, Penco, S, Petrucci, A, Piccirillo, G, Pirisi, A, Pisano, F, Pugliatti, M, Restagno, G, Ricci, C, Rita Murru, M, Riva, N, Sabatelli, M, Salvi, F, Santarelli, M, Sideri, R, Simone, I, Spataro, R, Tanel, R, Tedeschi, G, Tranquilli, S, Tremolizzo, L, Trojsi, F, Volanti, P, Zollino, M, Abramzon, Y, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Chia, R, Cooper‐Knock, J, Cusi, D, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, Faghri, F, Feldman, E, Kay Floeter, M, Fratta, P, Geiger, JT, Gerhard, G, Gibbs, JR, Gibson, SB, Glass, JD, Hardy, J, Harms, MB, Heiman‐Patterson, TD, Hernandez, DG, Jansson, L, Kamel, F, Kirby, J, Kowall, NW, Laaksovirta, H, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering‐Brown, S, Pioro, E, Pliner, HA, Pulst, SM, Ravits, JM, Renton, AE, Rivera, A, Robbrecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Salvi, E, Scholz, SW, Sendtner, M, Shaw, PJ, Sidle, KC, Simmons, Z, Singleton, AB, Stone, DC, Sulkava, R, Tienari, PJ, Traynor, BJ, Trojanowski, JQ, Troncoso, JC, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Stone, DJ, Bandres-Ciga, Sara, Noyce, Alastair J., Hemani, Gibran, Nicolas, Aude, Calvo, Andrea, Mora, Gabriele, Arosio, Alessandro, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Benigni, Michele, Borghero, Giuseppe, Brunetti, Maura, Cammarosano, Stefania, Cannas, Antonino, Canosa, Antonio, Capasso, Margherita, Caponnetto, Claudia, Caredda, Carla, Carrera, Paola, Casale, Federico, Cavallaro, Sebastiano, Chiò, Adriano, Colletti, Tiziana, Conforti, Francesca L., Conte, Amelia, Corrado, Lucia, Costantino, Emanuela, D'Alfonso, Sandra, Fasano, Antonio, Femiano, Cinzia, Ferrarese, Carlo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Giannini, Fabio, Grassano, Maurizio, Ilardi, Antonio, La Bella, Vincenzo, Lattante, Serena, Logroscino, Giancarlo, Logullo, Francesco O., Loi, Daniela, Lunetta, Christian, Mancardi, Gianluigi, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Marangi, Giuseppe, Marinou, Kalliopi, Marrali, Giuseppe, Marrosu, Maria Giovanna, Mazzini, Letizia, Melis, Maurizio, Messina, Sonia, Moglia, Cristina, Monsurro, Maria Rosaria, Mosca, Lorena, Occhineri, Patrizia, Origone, Paola, Pani, Carla, Penco, Silvana, Petrucci, Antonio, Piccirillo, Giovanni, Pirisi, Angelo, Pisano, Fabrizio, Pugliatti, Maura, Restagno, Gabriella, Ricci, Claudia, Rita Murru, Maria, Riva, Nilo, Sabatelli, Mario, Salvi, Fabrizio, Santarelli, Marialuisa, Sideri, Riccardo, Simone, Isabella, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Volanti, Paolo, Zollino, Marcella, Abramzon, Yevgeniya, Arepalli, Sampath, Baloh, Robert H., Bowser, Robert, Brady, Christopher B., Brice, Alexi, Broach, Jame, Campbell, Roy H., Camu, William, Chia, Ruth, Cooper-Knock, John, Cusi, Daniele, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Eicher, John D., Faghri, Faraz, Feldman, Eva, Kay Floeter, Mary, Fratta, Pietro, Geiger, Joshua T., Gerhard, Glenn, Gibbs, J. Raphael, Gibson, Summer B., Glass, Jonathan D., Hardy, John, Harms, Matthew B., Heiman-Patterson, Terry D., Hernandez, Dena G., Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J. L., Maragakis, Nicholas J., Mouzat, Kevin, Murphy, Natalie A., Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik, Pliner, Hannah A., Pulst, Stefan M., Ravits, John M., Renton, Alan E., Rivera, Alberto, Robbrecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D., Salvi, Erika, Scholz, Sonja W., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Singleton, Andrew B., Stone, David C., Sulkava, Raimo, Tienari, Pentti J., Traynor, Bryan J., Trojanowski, John Q., Troncoso, Juan C., Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Stone, David J., Van Damme, P, Bandres-Ciga, S, Noyce, A, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Tienari, P, Stone, D, Nalls, M, Singleton, A, Chiò, A, Traynor, Bryan, J, Tremolizzo, L, Department of Neurosciences, Neurologian yksikkö, Clinicum, HUS Neurocenter, Translational neuroradiology unit [Bethesda], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada, Spain, Partenaires INRAE, Queen Mary University of London (QMUL), University College of London [London] (UCL), University of Bristol [Bristol], Département de Physique, Université de Genève, Université de Genève (UNIGE), Università degli studi di Torino (UNITO), University G. d'Annunzio, Chieti, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Department of Health Sciences, UPO University, UPO University, Dipartimento di Matematica 'Ulisse Dini', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Neurology, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Department of Neuroscience, University of Siena, Siena, Università cattolica del Sacro Cuore [Roma] (Unicatt), Università degli studi di Bari Aldo Moro (UNIBA), Istituto di Genetica Medica, Centro Sclerosi Multipla, Ospedale Binaghi, Via Is Guadazzonis 2, Cagliari, Italy, University of Novara, IRCCS-Istituti Clinici Scientifici Maugeri, University of Milan, Milan, Italy, Department of Biomedical and Specialty Surgical Sciences, Università degli Studi di Ferrara (UniFE), S. Anna Hospital, Department of Neuroscience, Catholic University, Roma, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Medical Genetics, Catholic University, Rome, Italy, Department of Clinical Genetics, Department of Pathology University of Pittsburgh School of Medicine, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Princeton University, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Milano [Milano] (UNIMI), Laboratory of Neurogenetics, National Institute of Aging, Tel Aviv Sourasky Medical Center [Te Aviv], University of New Haven [Connecticut], Emory University [Atlanta, GA], UCL Institute of neurology, UCL Institute of Neurology, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Boston University [Boston] (BU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California-University of California, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Johns Hopkins University, School of Medicine, Department of Medicine, Surgery, and Dentistry, University of Milano, Institute for Clinical Neurobiology, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Penn State Hershey Medical Center, Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System-Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Metacohorts Consortium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Helsinki, Merck Research Laboratories, National Institutes of Health [Bethesda] (NIH), Center for Neuroscience and Regenerative Medicine [Bethesda] (CNRM), and Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM)
Subjects: 0301 basic medicine, Linkage disequilibrium, Multifactorial Inheritance, Multivariate analysis, LD SCORE REGRESSION, DYSLIPIDEMIA, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, PROTECTIVE FACTOR, Mendelian Randomization Analysis, 3. Good health, ALZHEIMERS-DISEASE, Settore MED/26 - NEUROLOGIA, risk factor, BIAS, Neurology, CARDIOVASCULAR-DISEASE, MENDELIAN RANDOMIZATION, Amyotrophic lateral Sclerosis, LD score regression, Mendelian randomization, amyotrophic lateral sclerosis, public resource, Life Sciences & Biomedicine, Clinical psychology, Human, Clinical Neurology, Biology, NO, 03 medical and health sciences, Humans, Genetic Predisposition to Disease, Mendelian Randomization Analysi, MESH: Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease / genetics, Genome-Wide Association Study / methods, Mendolian Randomization Analysis / methods, Exercise, Genetic association, Science & Technology, [SCCO.NEUR]Cognitive science/Neuroscience, Amyotrophic Lateral Sclerosis, 3112 Neurosciences, Neurosciences, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, CHOLESTEROL HOMEOSTASIS, Causal inference, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurosciences & Neurology, Neurology (clinical), Genome-Wide Association Study, ALS, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract: OBJECTIVE: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). METHODS: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. RESULTS: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. INTERPRETATION: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470-481. ispartof: ANNALS OF NEUROLOGY vol:85 issue:4 pages:470-481 ispartof: location:United States status: published
Published: 2019
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30. Germline pathogenic variant in PIK3CA leading to symmetrical overgrowth with marked macrocephaly and mild global developmental delay

Author: Zollino, Marcella, Ranieri, C., Grossi, V., Leoni, Chiara, Lattante, Serena, Mazza', Daniela, Simone, C., Resta, N., Zollino M. (ORCID:0000-0003-4871-9519), Leoni C., Lattante S. (ORCID:0000-0003-2891-0340), Mazza D., Zollino, Marcella, Ranieri, C., Grossi, V., Leoni, Chiara, Lattante, Serena, Mazza', Daniela, Simone, C., Resta, N., Zollino M. (ORCID:0000-0003-4871-9519), Leoni C., Lattante S. (ORCID:0000-0003-2891-0340), and Mazza D.
Abstract: Background: Activating pathogenic variants in PIK3CA gene usually occur at a mosaic status and underlie a variety of segmental overgrowth phenotypes. Germline variants in PIK3CA have been rarely reported, described in a total of 12 patients with macrocephaly to date. Clinical and prognostic features of these germline variants have not been described in detail yet. Methods: Targeted deep sequencing by custom panel of the 21 genes involved in the PI3K/AKT/mTOR pathway was performed in a 13-year-old boy with macrocephaly and physical overgrowth. PI3K/AKT/mTOR pathway analysis was performed in fibroblasts by Western blot. The effects of miransertib (AKT inhibitor) and rapamycin (mTOR inhibitor) were assessed. Results: A de novo pathogenic variant (c.1090G>C; p.Gly364Arg) in PIK3CA gene was detected in a non-mosaic status in peripheral blood cells, buccal smears, and skin fibroblasts. Increased levels of phosphorylated AKT residues were observed in fibroblasts, rescued by miransertib. Conclusion: Germline variants in PIK3CA are associated to a mild phenotype characterized by overgrowth, severe macrocephaly, mild intellectual disability, and few dysmorphic features. Investigations of PI3K/AKT/mTOR pathway should be performed in patients with severe macrocephaly and unspecific physical overgrowth. Longitudinal studies to assess prognosis and cancer predisposition are recommended.
Published: 2019

31. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Author: Bandres-Ciga, S., Noyce, A. J., Hemani, G., Nicolas, A., Calvo, A., Mora, G., Arosio, A., Barberis, M., Bartolomei, I., Battistini, S., Benigni, M., Borghero, G., Brunetti, M., Cammarosano, S., Cannas, A., Canosa, A., Capasso, Monica, Caponnetto, C., Caredda, C., Carrera, P., Casale, F., Cavallaro, S., Chio, A., Colletti, T., Conforti, F. L., Conte, Amelia, Corrado, L., Costantino, E., D'Alfonso, Sandra, Fasano, Alfonso, Femiano, C., Ferrarese, C., Fini, N., Floris, G., Fuda, G., Giannini, F., Grassano, M., Ilardi, A., La Bella, V., Lattante, Serena, Logroscino, Giandomenico, Logullo, F. O., Loi, D., Lunetta, C., Mancardi, G., Mandich, P., Mandrioli, J., Manera, U., Marangi, Giuseppe, Marinou, K., Marrali, G., Marrosu, M. G., Mazzini, L., Melis, M., Messina, S., Moglia, C., Monsurro, M. R., Mosca, Luigi, Occhineri, P., Origone, P., Pani, C., Penco, S., Petrucci, A., Piccirillo, G., Pirisi, A., Pisano, F., Pugliatti, M., Restagno, G., Ricci, C., Rita Murru, M., Riva, N., Sabatelli, Mario, Salvi, F., Santarelli, M., Sideri, R., De Simone, Idor, Spataro, R., Tanel, R., Tedeschi, G., Tranquilli, S., Tremolizzo, L., Trojsi, F., Volanti, P., Zollino, Marcella, Abramzon, Y., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Cusi, D., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., Faghri, F., Feldman, E., Kay Floeter, M., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kamel, F., Kirby, J., Kowall, N. W., Laaksovirta, H., Landi, Francesco, Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robbrecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Salvi, E., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Stone, D. C., Sulkava, R., Tienari, P. J., Traynor, B. J., Trojanowski, J. Q., Troncoso, J. C., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Stone, D. J., Capasso M., Conte A., D'Alfonso S., Fasano A., Lattante S. (ORCID:0000-0003-2891-0340), Logroscino G. (ORCID:0000-0003-1301-5343), Marangi G. (ORCID:0000-0002-6898-8882), Mosca L. (ORCID:0000-0003-4641-0841), Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Landi F. (ORCID:0000-0002-3472-1389), Bandres-Ciga, S., Noyce, A. J., Hemani, G., Nicolas, A., Calvo, A., Mora, G., Arosio, A., Barberis, M., Bartolomei, I., Battistini, S., Benigni, M., Borghero, G., Brunetti, M., Cammarosano, S., Cannas, A., Canosa, A., Capasso, Monica, Caponnetto, C., Caredda, C., Carrera, P., Casale, F., Cavallaro, S., Chio, A., Colletti, T., Conforti, F. L., Conte, Amelia, Corrado, L., Costantino, E., D'Alfonso, Sandra, Fasano, Alfonso, Femiano, C., Ferrarese, C., Fini, N., Floris, G., Fuda, G., Giannini, F., Grassano, M., Ilardi, A., La Bella, V., Lattante, Serena, Logroscino, Giandomenico, Logullo, F. O., Loi, D., Lunetta, C., Mancardi, G., Mandich, P., Mandrioli, J., Manera, U., Marangi, Giuseppe, Marinou, K., Marrali, G., Marrosu, M. G., Mazzini, L., Melis, M., Messina, S., Moglia, C., Monsurro, M. R., Mosca, Luigi, Occhineri, P., Origone, P., Pani, C., Penco, S., Petrucci, A., Piccirillo, G., Pirisi, A., Pisano, F., Pugliatti, M., Restagno, G., Ricci, C., Rita Murru, M., Riva, N., Sabatelli, Mario, Salvi, F., Santarelli, M., Sideri, R., De Simone, Idor, Spataro, R., Tanel, R., Tedeschi, G., Tranquilli, S., Tremolizzo, L., Trojsi, F., Volanti, P., Zollino, Marcella, Abramzon, Y., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Cusi, D., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., Faghri, F., Feldman, E., Kay Floeter, M., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kamel, F., Kirby, J., Kowall, N. W., Laaksovirta, H., Landi, Francesco, Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robbrecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Salvi, E., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Stone, D. C., Sulkava, R., Tienari, P. J., Traynor, B. J., Trojanowski, J. Q., Troncoso, J. C., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Stone, D. J., Capasso M., Conte A., D'Alfonso S., Fasano A., Lattante S. (ORCID:0000-0003-2891-0340), Logroscino G. (ORCID:0000-0003-1301-5343), Marangi G. (ORCID:0000-0002-6898-8882), Mosca L. (ORCID:0000-0003-4641-0841), Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), and Landi F. (ORCID:0000-0002-3472-1389)
Abstract: Objective: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). Methods: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. Results: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. Interpretation: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470–481.
Published: 2019

32. Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers

Author: Fournier, C., Barbier, M., Camuzat, A., Anquetil, V., Lattante, Serena, Clot, F., Cazeneuve, C., Rinaldi, D., Couratier, P., Deramecourt, V., Sabatelli, Mario, Belliard, S., Vercelletto, M., Forlani, S., Jornea, L., Brice, A., Auriacombe, S., Blanc, F., Bouteleau-Bretonniere, C., Ceccaldi, M., Didic, M., Dubois, B., Duyckaerts, C., Etcharry-Bouix, F., Golfier, V., Hannequin, D., Lacomblez, L., Le Ber, I., Levy, R., Michel, B. -F., Pasquier, F., Thomas-Anterion, C., Pariente, J., Sellal, F., Benchetrit, E., Bertin, H., Bertrand, A., Bissery, A., Bombois, S., Boncoeur, M. -P., Cassagnaud, P., Chastan, M., Chen, Y., Chupin, M., Colliot, O., Delbeucq, X., Delmaire, C., Gerardin, E., Hossein-Foucher, C., Habert, M. -O., Lautrette, G., Lebouvier, T., Lehericy, S., Le Toullec, B., Martineau, K., Mackowiak, M. -A., Monteil, J., Petyt, G., Pradat, P. -F., Oya, A. -H., Rollin-Sillaire, A., Salachas, F., Sayah, S., Wallon, D., Leguern, E., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Fournier, C., Barbier, M., Camuzat, A., Anquetil, V., Lattante, Serena, Clot, F., Cazeneuve, C., Rinaldi, D., Couratier, P., Deramecourt, V., Sabatelli, Mario, Belliard, S., Vercelletto, M., Forlani, S., Jornea, L., Brice, A., Auriacombe, S., Blanc, F., Bouteleau-Bretonniere, C., Ceccaldi, M., Didic, M., Dubois, B., Duyckaerts, C., Etcharry-Bouix, F., Golfier, V., Hannequin, D., Lacomblez, L., Le Ber, I., Levy, R., Michel, B. -F., Pasquier, F., Thomas-Anterion, C., Pariente, J., Sellal, F., Benchetrit, E., Bertin, H., Bertrand, A., Bissery, A., Bombois, S., Boncoeur, M. -P., Cassagnaud, P., Chastan, M., Chen, Y., Chupin, M., Colliot, O., Delbeucq, X., Delmaire, C., Gerardin, E., Hossein-Foucher, C., Habert, M. -O., Lautrette, G., Lebouvier, T., Lehericy, S., Le Toullec, B., Martineau, K., Mackowiak, M. -A., Monteil, J., Petyt, G., Pradat, P. -F., Oya, A. -H., Rollin-Sillaire, A., Salachas, F., Sayah, S., Wallon, D., Leguern, E., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)
Abstract: A (GGGGCC) n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10 e−4 ) but our results suggested that the association was mainly driven by age at collection (p < 10 e−4 ). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers.
Published: 2019

33. Generation of induced pluripotent stem cells (CSSi017-A)(12862) from an ALS patient carrying a repeat expansion in the C9orf72 gene.

Author: Ruotolo, G., D'Anzi, A., Casamassa, A., Mazzoni, M., Ferrari, D., Lombardi, I., Carletti, R.M., D'Asdia, C., Torrente, I., Frezza, K., Lattante, S., Sabatelli, M., Pennuto, M., Vescovi, A.L., and Rosati, J.
Abstract: Genetic expansions of the hexanucleotide repeats (GGGGCC) in the C9orf72 gene appear in approximately 40% of patients with familial ALS and 7% of patients with sporadic ALS in the European population, making this mutation one of the most prevalent genetic mutations in ALS. Here, we generated a human induced pluripotent stem cell (hiPSC) line from the dermal fibroblasts of a patient carrying a 56-repeat expansion in an ALS disease-causing allele of C9orf72. These iPSCs showed stable amplification in vitro with normal karyotype and high expression of pluripotent markers and differentiated spontaneously in vivo into three germ layers. [ABSTRACT FROM AUTHOR]
Published: 2024
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34. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick, Pliner, Hannah A., Shankaracharya, null, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Mazzini, Letizia, Messina, Sonia, D'Alfonso, Sandra, Corrado, Lucia, Ferrucci, Luigi, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, George, Appel, Stanley, Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard S., Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Allen, Andrew S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steven, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Wyman, Stacia K., Van Eyk, Jennifer E., Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L. M. A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J. L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Mattieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Basak, A. 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Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

35. HFE p.H63D polymorphism does not influence ALS phenotype and survival

Author: Chio, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Monsurro, M, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Nilo, R, Giannini, F, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Zollino, M, Conforti, F, Penco, S, Brunetti, M, Barberis, M, Restagno, G, Logroscino, G, Bartolomei, I, Capasso, M, Mancardi, G, Origone, P, Marinou, K, Sideri, R, Mosca, L, Pinter, G, Corbo, M, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Battistini, S, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, Chio A., Mora G., Sabatelli M., Caponnetto C., Lunetta C., Traynor B. J., Johnson J. O., Nalls M. A., Calvo A., Moglia C., Borghero G., Monsurro M. R., La Bella V., Volanti P., Simone I., Salvi F., Logullo F. O., Nilo R., Giannini F., Mandrioli J., Tanel R., Murru M. R., Mandich P., Zollino M., Conforti F. L., Penco S., Brunetti M., Barberis M., Restagno G., Logroscino G., Bartolomei I., Capasso M., Mancardi G., Origone P., Marinou K., Sideri R., Mosca L., Pinter G. L., Corbo M., Fini N., Georgoulopoulou E., Tremolizzo L., Tedeschi G., Trojsi F., Piccirillo G., Cristillo V., Spataro R., Colletti T., Conte A., Luigetti M., Lattante S., Marangi G., Santarelli M., Petrucci A., Battistini S., Ricci C., Benigni M., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Ilardi A., Bertuzzo D., Pisano F., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M. G., Floris G., Cannas A., Ticca A., Pugliatti M., Pirisi A., Parish L. D., Occhineri P., Ortu E., Cau T. B., Loi D., Chio, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Monsurro, M, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Nilo, R, Giannini, F, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Zollino, M, Conforti, F, Penco, S, Brunetti, M, Barberis, M, Restagno, G, Logroscino, G, Bartolomei, I, Capasso, M, Mancardi, G, Origone, P, Marinou, K, Sideri, R, Mosca, L, Pinter, G, Corbo, M, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Battistini, S, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, Chio A., Mora G., Sabatelli M., Caponnetto C., Lunetta C., Traynor B. J., Johnson J. O., Nalls M. A., Calvo A., Moglia C., Borghero G., Monsurro M. R., La Bella V., Volanti P., Simone I., Salvi F., Logullo F. O., Nilo R., Giannini F., Mandrioli J., Tanel R., Murru M. R., Mandich P., Zollino M., Conforti F. L., Penco S., Brunetti M., Barberis M., Restagno G., Logroscino G., Bartolomei I., Capasso M., Mancardi G., Origone P., Marinou K., Sideri R., Mosca L., Pinter G. L., Corbo M., Fini N., Georgoulopoulou E., Tremolizzo L., Tedeschi G., Trojsi F., Piccirillo G., Cristillo V., Spataro R., Colletti T., Conte A., Luigetti M., Lattante S., Marangi G., Santarelli M., Petrucci A., Battistini S., Ricci C., Benigni M., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Ilardi A., Bertuzzo D., Pisano F., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M. G., Floris G., Cannas A., Ticca A., Pugliatti M., Pirisi A., Parish L. D., Occhineri P., Ortu E., Cau T. B., and Loi D.
Abstract: It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients.
Published: 2015

36. Genetic counselling in ALS: facts, uncertainties and clinical suggestions

Author: Chio, A., Battistini, Stefania, Calvo, A., Caponnetto, C., Conforti, F. L., Corbo, M., Giannini, Fabio, Mandrioli, J., Mora, G., Sabatelli, M., Ajmone, C., Mastro, E., Pain, D., Mandich, P., Penco, S., Restagno, G., Zollino, M., Surbone, A., Monsurro, M. R., Tedeschi, G., Conte, A., Luigetti, M., Lattante, S., Marangi, G., Volanti, P., Marinou, K., Papetti, L., Lunetta, C., Pintor, G. L., Salvi, F., Bartolomei, I., Quattrone, A., Gambardella, A., Logroscino, G., Simone, I., Pisano, F., Spataro, R., La Bella, V., Colletti, T., Mancardi, G., Origone, P., Sola, P., Borghero, G., Marrosu, F., Marrosu, M. G., Murru, M. R., Floris, G., Cannas, A., Piras, V., Costantino, E., Pani, C., Sotgiu, M. A., Pugliatti, M., Parish, L. D., Cossu, P., Ticca, A., Rodolico, C., Portaro, S., Ricci, Claudia, Moglia, C., Ossola, I., Brunetti, M., Barberis, M., Canosa, A., Cammarosano, S., Bertuzzo, D., Fuda, G., Ilardi, A., Manera, U., Pastore, I., Sproviero, W., Logullo, F., Tanel, R., Chiò, A, Battistini, S, Calvo, A, Caponnetto, C, Conforti, FL, Corbo, M, Giannini, F, Mandrioli, J, Mora, G, Sabatelli, M, Cammarosano, S, Canosa, A, Moglia, C, Ajmone, C, Mastro, E, Pain, D, Mandich, P, Penco, S, Restagno, G, Zollino, M, Surbone, A, Conforti, Fl, Italsgen, Consortium, Among, Collaborator, Tedeschi, Gioacchino, and Surbone, A.
Subjects: medicine.medical_specialty, Genotype, GENETICS, Genetic counseling, Genetic Counseling, Gene mutation, Settore MED/03 - GENETICA MEDICA, medicine, Humans, Genetic Testing, Amyotrophic lateral sclerosis, Genetic discrimination, Psychiatry, Genetic testing, medicine.diagnostic_test, business.industry, Amyotrophic Lateral Sclerosis, medicine.disease, Penetrance, ALS, 3. Good health, Psychiatry and Mental health, Phenotype, Frontotemporal Dementia, Mutation, Surgery, Settore MED/26 - Neurologia, Neurology (clinical), business, Motor neurone disease, Frontotemporal dementia
Abstract: The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination.
Published: 2014
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37. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B. J, Johnson, J. O, Nalls, M. A, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F. O, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M. R, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F. L, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M. R, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M. G, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L. D, Occhineri, P, Ortu, E, Cau, T. B, Loi, D, Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Lunetta, C., Traynor, B., Johnson, J., Nalls, M., Calvo, A., Moglia, C., Borghero, G., Trojsi, F., LA BELLA, V., Volanti, P., Simone, I., Salvi, F., Logullo, F., Riva, N., Carrera, P., Giannini, F., Mandrioli, J., Tanel, R., Capasso, M., Tremolizzo, L., Battistini, S., Murru, M., Origone, P., Zollino, M., Penco, S., Mazzini, L., D'Alfonso, S., Restagno, G., Brunetti, M., Barberis, M., Conforti, F., Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Lunetta, Christian, Traynor, Bryan J, Johnson, Janel O, Nalls, Mike A, Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Trojsi, Francesca, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O, Riva, Nilo, Carrera, Paola, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Capasso, Margherita, Tremolizzo, Lucio, Battistini, Stefania, Murru, Maria Rita, Origone, Paola, Zollino, Marcella, Penco, Silvana, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Pinter, Gl, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, Gioacchino, Monsurro', Maria Rosaria, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, Mg, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, Ld, Occhineri, P, Ortu, E, Cau, Tb, Loi, D, Mazzini, Letizia, D'Alfonso, Sandra, Restagno, Gabriella, Brunetti, Maura, Barberis, Marco, Conforti, Francesca L., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Lauria Pinter, G, Tedeschi, G, Monsurrò, M, Marrosu, M, Parish, L, and Cau, T
Subjects: Male, 0301 basic medicine, Aging, C9ORF72, Genetic Association Studie, 030105 genetics & heredity, Biology, Settore MED/03 - GENETICA MEDICA, 03 medical and health sciences, 0302 clinical medicine, C9orf72, medicine, Allele, Amyotrophic lateral sclerosis, Amyotrophic lateral sclerosi, Aged, Ataxin-2, Regulator gene, ATXN2, Phenotype, Neuroscience (all), Medicine (all), Developmental Biology, Geriatrics and Gerontology, Neurology (clinical), Genetics, DNA Repeat Expansion, Protein, General Neuroscience, Middle Aged, medicine.disease, 3. Good health, C9orf72 Protein, Italy, Population study, Female, Settore MED/26 - Neurologia, Trinucleotide repeat expansion, 030217 neurology & neurosurgery, Human
Abstract: There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non- C9ORF72 mutated patients.
Published: 2015
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38. Interplay between stimulated emission and singlet-singlet annihilation in oligothiophene dioxide thin films.

Author: Lattante, S., De Giorgi, M., Barbarella, G., Favaretto, L., Gigli, G., Cingolani, R., and Anni, M.
Subjects: *THIN films, *SURFACES (Technology), *LIGHT emitting diodes, *SEMICONDUCTOR diodes, *FIELD-effect transistors, *PHOTOLUMINESCENCE
Abstract: We have studied the optical properties of different thienyl-S,S-dioxide oligothiophenes under strong excitation. No stimulated emission is observed in neat films due to singlet-singlet bimolecular annihilation. The bimolecular recombination constant is quantified from a rate equation model in the limit of constant annihilation rate. We demonstrate that tunable stimulated emission in the range 490–660 nm, due to optical gain with an estimated cross section of the order of σg≈10-17 cm2, can be obtained by blending the active molecule with small quantities of inert polycarbonate poly(bisphenol-A-carbonate) (PC). The presence of amplified spontaneous emission (ASE) for a PC:active molecule relative concentration as small as 1:500 suggests that the polycarbonate role is to reduce the intermolecular diffusion rate rather than to isolate the active molecules. Moreover, for higher PC content, a continuous decrease of the bimolecular quenching role is observed. These results demonstrate that the absence of stimulated emission in neat films is not necessarily due to intrinsic molecular properties, as strong ASE can be obtained by slightly modifying the molecule interaction during the deposition process. This approach could allow a considerable extension of the number of molecules showing stimulated emission for organic laser applications. [ABSTRACT FROM AUTHOR]
Published: 2006
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39. The role of excitons’ quasiequilibrium in the temperature dependence of the poly(9,9-dioctylfluorene) β phase photoluminescence.

Author: Anni, M., Caruso, M. E., Lattante, S., and Cingolani, R.
Subjects: FLUOROPOLYMERS, EXCITON theory, PHOTOLUMINESCENCE, TETRAHYDROFURAN, LIGHT absorption
Abstract: We investigated the temperature dependence of the poly(9,9-dioctylfluorene) β phase photoluminescence (PL) spectra in spin coated thin films from tetrahydrofuran solutions. As the temperature increases from 18 to 300 K a continuous blueshift of the 0-0 PL peak of about 25 meV and an increase of the peak full width at half maximum (FWHM) of about 49 meV are observed. We show that the PL spectra temperature dependence is not due to a temperature dependent average conjugation length, as often assumed, but instead it can be quantitatively explained in the frame of a thermal quasiequilibrium model for excitons in an inhomogeneously broadened excited states distribution. We demonstrate that the emission blueshift and broadening are mainly due to the increase of the excitons’ temperature with the sample one. This effect is partially compensated by an increasing efficiency of the exciton energy migration. The interplay between these two processes quantitatively explains the observed temperature dependence of the PL peak energy and of its FWHM. On the contrary we show that the PL spectra are almost independent of the absorption blueshift with temperature. [ABSTRACT FROM AUTHOR]
Published: 2006
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40. THE HFE HIS63ASP POLYMORPHISM IS A MODIFIER OF ALS OUTCOMES IN ITALIAN AND FRENCH PATIENTS WITH SOD1 MUTATIONS

Author: Chio, A, Mora, G, Lunetta, C, Brunetti, M, Barberis, M, Borghero, G, Tarlarini, C, Monsurro`, Mr, Zollino, M, Volanti, P, Italsgen, Lattante, S, Meiniger, V, Riva, N, Clavelou, P, Giannini, F, Mandrioli, J, Penco, S, Sabatelli, M, and Camu, W
Published: 2016

41. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

Author: Majounie, E1, Renton, Ae, Mok, K, Dopper, Eg, Waite, A, Rollinson, S, Chiò, A, Restagno, G, Nicolaou, N, Simon-Sanchez, J, van Swieten JC, Abramzon, Y, Johnson, Jo, Sendtner, M, Pamphlett, R, Orrell, Rw, Mead, S, Sidle, Kc, Houlden, H, Rohrer, Jd, Morrison, Ke, Pall, H, Talbot, K, Ansorge, O, Hernandez, Dg, Arepalli, S, Sabatelli, M, Mora, G, Corbo, M, Giannini, F, Calvo, A, Englund, E, Borghero, G, Floris, Gl, Remes, Am, Laaksovirta, H, Mccluskey, L, Trojanowski, Jq, Van Deerlin VM, Schellenberg, Gd, Nalls, Ma, Drory, Ve, Lu, Cs, Yeh, Th, Ishiura, H, Takahashi, Y, Tsuji, S, Le Ber, I, Brice, A, Drepper, C, Williams, N, Kirby, J, Shaw, P, Hardy, J, Tienari, Pj, Heutink, P, Morris, Hr, Pickering-Brown, S, Traynor, Bj, Adamson, G, Bayer, Aj, Beck, J, Callister, Jb, Blake, Dj, Blumen, Sc, Collinge, J, Dunckley, T, Ealing, J, East, S, Elman, L, Gerhard, A, Guerreiro, Rj, Gwinn, K, Halliwell, N, Hamdalla, Hh, Hewitt, C, Ince, P, Jablonka, S, James, C, Kent, L, Knock, Jc, Lynch, T, Mahoney, C, Mann, D, Neal, J, Norris, D, O'Dowd, S, Richardson, A, Rossor, M, Rothstein, J, Scholz, Sw, Snowden, J, Stephan, Da, Toulson, G, Turner, Mr, Warren, Jd, Young, K, Weng, Yh, Kuo, Hc, Lai, Sc, Huang, Cl, Camuzat, A, Entraingues, L, Guillot-Noël, Verpillat, P, Blanc, F, Camu, W, Clerget-Darpoux, F, Corcia, P, Couratier, P, Didic, M, Dubois, B, Duyckaerts, C, Guedj, E, Golfier, V, Habert, Mo, Hannequin, D, Lacomblez, L, Meininger, V, Salachas, F, Levy, R, Michel, Bf, Pasquier, F, Puel, M, Thomas-Anterion, C, Sellal, F, Vercelletto, M, Moglia, C, Cammarosano, S, Canosa, A, Gallo, S, Brunetti, M, Ossola, I, Marinou, K, Papetti, L, Pisano, F, Pinter, Gl, Conte, A, Luigetti, M, Zollino, M, Lattante, S, Marangi, G, la Bella, V, Spataro, R, Colletti, T, Battistini, S, Ricci, C, Caponnetto, C, Mancardi, G, Mandich, P, Salvi, F, Bartolomei, I, Mandrioli, J, Sola, P, Lunetta, C, Penco, S, Monsurrò, Mr, Tedeschi, G, Conforti, Fl, Gambardella, A, Quattrone, A, Volanti, P, Floris, G, Cannas, A, Piras, V, Marrosu, F, Marrosu, Mg, Murru, Mr, Pugliatti, M, Parish, Ld, Sotgiu, A, Solinas, G, Ulgheri, L, Ticca, A, Simone, I, Logroscino, G., Neurology, Erasmus MC other, The Chromosome 9-ALS/FTD Consortium, Human genetics, NCA - Neurodegeneration, Università degli studi di Torino (UNITO), Department of Clinical Genetics, Institute for Clinical Neurobiology, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), MRC Prion Unit, UCL Institute of neurology, UCL Institute of Neurology, UCL Institute of Neurology, Queen Square, London, Department of Neuroscience, Catholic University, Roma, Fondazione Maugeri, Department of Neuroscience, University of Siena, Siena, Department of Neurology, Chang Gung Memorial Hospital [Taipei] (CGMH), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Università degli studi di Torino = University of Turin (UNITO), Julius-Maximilians-Universität Würzburg (JMU), UCL Institute of Neurology, Queen Square [London], Università degli Studi di Siena = University of Siena (UNISI), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH: Signal Transduction, Male, MESH: Vesicular Transport Proteins, MESH: Membrane Glycoproteins, MESH: DNA Repeat Expansion, MESH: Genotype, Cohort Studies, MESH: Protein Structure, Tertiary, MESH: Aged, 80 and over, MESH: Interferon Regulatory Factor-3, 0302 clinical medicine, C9orf72, MESH: Child, MESH: RNA, Small Interfering, 80 and over, genetics, Age of Onset, Child, MESH: Cohort Studies, MESH: Amyotrophic Lateral Sclerosis, MESH: Aged, Genetics, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, DNA Repeat Expansion, MESH: Toll-Like Receptor 4, Middle Aged, Penetrance, 3. Good health, Settore MED/26 - NEUROLOGIA, Neurology, MESH: Young Adult, MESH: HEK293 Cells, Child, Preschool, Frontotemporal Dementia, Female, Sample collection, Chromosomes, Human, Pair 9, MESH: Myeloid Differentiation Factor 88, Frontotemporal dementia, Human, Pair 9, Adult, MESH: Protein Transport, medicine.medical_specialty, Adolescent, Genotype, MESH: Age of Onset, MESH: RNA Interference, Clinical Neurology, MESH: Frontotemporal Dementia, MESH: Genetic Loci, TARDBP, Chromosomes, 03 medical and health sciences, Open Reading Frames, Young Adult, MESH: Cross-Sectional Studies, Internal medicine, medicine, MESH: Chemokine CCL5, Humans, ddc:610, Preschool, MESH: Adaptor Proteins, Signal Transducing, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Transfection, MESH: Child, Preschool, Haplotype, Amyotrophic Lateral Sclerosis, MESH: Adult, MESH: Adaptor Proteins, Vesicular Transport, MESH: Open Reading Frames, medicine.disease, MESH: Male, MESH: Cell Line, C9orf72 Protein, Cross-Sectional Studies, MESH: Endosomes, Genetic Loci, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), MESH: Lipopolysaccharides, MESH: Chromosomes, Human, Pair 9, business, Trinucleotide repeat expansion, MESH: Female, Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, genetics, Child, Child, Preschool, Chromosomes, genetics, Cohort Studies, Cross-Sectional Studies, DNA Repeat Expansion, genetics, Female, Frontotemporal Dementia, genetics, Genetic Loci, Genotype, Humans, Male, Middle Aged, Open Reading Frames, genetics, Young Adult, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). METHODS: We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. FINDINGS: In patients with sporadic ALS, we identified the repeat expansion in 236 (7*0%) of 3377 white individuals from the USA, Europe, and Australia, two (4*1%) of 49 black individuals from the USA, and six (8*3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39*3%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6*0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24*8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. INTERPRETATION: A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
Published: 2012
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42. CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Traynor, B. J, Johnson, J. O, Nalls, M. A, Calvo, A, Moglia, C, Borghero, G, Monsurrò, M. R, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F. O, Nilo, R, Battistini, S, Mandrioli, J, Tanel, R, Murru, M. R, Mandich, P, Zollino, M, Conforti, F. L, Brunetti, M, Barberis, M, Restagno, G, Penco, S, Lunetta, C, Giannini, F, Ricci, C, Mancardi, G, Bartolomei, I, Corbo, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Ossola, I, Logroscino, G, Tedeschi, G, Pugliatti, M, Pinter, G. L, Glynn, S, Gibbs, J. R, Cammarosano, S, Canosa, A, Manera, U, Bertuzzo, D, Ilardi, A, Marinou, K, Sideri, R, Pisano, F, Spataro, R, Colletti, T, Floris, G, Cannas, A, Piras, V, Marrosu, F, Marrosu, M. G, Parish, L. D, Ticca, A, Pirisi, A, Ortu, E, Cau, T. B, Loi, D, Traccis, S, Fini, N, Georgoulopoulou, E, Casale, F, Marrali, G, Fuda, G, Solamone, P, Maestri, E, Mazzei, R, Cristillo, V, Puddu, R, Costantino, E, Pani, C, Caredda, C, Origone, P, Mosca, L, Capasso, M, Turri, M, Petrucci, A, Tremolizzo, L, Santarelli, M., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Monsurrò, M, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Nilo, R, Battistini, S, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Zollino, M, Conforti, F, Brunetti, M, Barberis, M, Restagno, G, Penco, S, Lunetta, C, Giannini, F, Ricci, C, Mancardi, G, Bartolomei, I, Corbo, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Ossola, I, Logroscino, G, Tedeschi, G, Pugliatti, M, Pinter, G, Glynn, S, Gibbs, J, Cammarosano, S, Canosa, A, Manera, U, Bertuzzo, D, Ilardi, A, Marinou, K, Sideri, R, Pisano, F, Spataro, R, Colletti, T, Floris, G, Cannas, A, Piras, V, Marrosu, F, Marrosu, M, Parish, L, Ticca, A, Pirisi, A, Ortu, E, Cau, T, Loi, D, Traccis, S, Fini, N, Georgoulopoulou, E, Casale, F, Marrali, G, Fuda, G, Solamone, P, Maestri, E, Mazzei, R, Cristillo, V, Puddu, R, Costantino, E, Pani, C, Caredda, C, Origone, P, Mosca, L, Capasso, M, Turri, M, Petrucci, A, Tremolizzo, L, Santarelli, M, Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Monsurro', Maria Rosaria, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Nilo, Riva, Battistini, Stefania, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Zollino, Marcella, Conforti, Francesca L., Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Penco, Silvana, Lunetta, Christian, Giannini, Fabio, Ricci, Claudia, Mancardi, Gianluigi, Bartolomei, Ilaria, Corbo, Massimo, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Ossola, Irene, Logroscino, Giancarlo, Tedeschi, Gioacchino, Pugliatti, Maura, Pinter, Giuseppe Lauria, Glynn, Shannon, Gibbs, J. Raphael, Cammarosano, Stefania, Canosa, Antonio, Manera, Umberto, Bertuzzo, Davide, Ilardi, Altonio, Marinou, Kalliopi, Sideri, Riccardo, Pisano, Fabrizio, Spataro, Rossella, Colletti, Tiziana, Floris, Gianluca, Cannas, Antonino, Piras, Valeria, Marrosu, Francesco, Marrosu, Maria Giovanna, Parish, Leslie D., Ticca, Anna, Pirisi, Angelo, Ortu, Enzo, Cau, Tea B., Loi, Daniela, Traccis, Sebastiano, Fini, Nicola, Georgoulopoulou, Eleni, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Solamone, Paolina, Maestri, Eleonora, Mazzei, Rosalucia, Cristillo, Viviana, Puddu, Roberta, Costantino, Emanuela, Pani, Carla, Caredda, Carla, Origone, Paola, Mosca, Lorena, Capasso, Margherita, Turri, Mara, Petrucci, Antonio, Tremolizzo, Luico, Santarelli, Marialaura, Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Traynor, B., Johnson, J., Nalls, M., Calvo, A., Moglia, C., Borghero, G., Monsurrò, M., LA BELLA, V., Volanti, P., Simone, I., Salvi, F., Logullo, F., Nilo, R., Battistini, S., Mandrioli, J., Tanel, R., Murru, M., Mandich, P., Zollino, M., Conforti, F., Brunetti, M., Barberis, M., Restagno, G., Penco, S., Lunetta, C., Giannini, F., Ricci, C., Mancardi, G., Bartolomei, I., Corbo, M., Conte, A., Luigetti, M., Lattante, S., Marangi, G., Ossola, I., Logroscino, G., Tedeschi, G., Pugliatti, M., Pinter, G., Glynn, S., Gibbs, J., Cammarosano, S., Canosa, A., Manera, U., Bertuzzo, D., Ilardi, A., Marinou, K., Sideri, R., Pisano, F., Spataro, R., Colletti, T., Floris, G., Cannas, A., Piras, V., Marrosu, F., Marrosu, M., Parish, L., Ticca, A., Pirisi, A., Ortu, E., Cau, T., Loi, D., Traccis, S., Fini, N., Georgoulopoulou, E., Casale, F., Marrali, G., Fuda, G., Solamone, P., Maestri, E., Mazzei, R., Cristillo, V., Puddu, R., Costantino, E., Pani, C., Caredda, C., Origone, P., Mosca, L., Capasso, M., Turri, M., Petrucci, A., Tremolizzo, L., and Santarelli, M.
Subjects: Male, Aging, Pediatrics, medicine.medical_specialty, Pathology, Amyotrophic lateral sclerosis, CHCHD10, Familial, Sporadic, Aged, Amyotrophic Lateral Sclerosis, Cohort Studies, Female, Frontotemporal Dementia, Genetic Predisposition to Disease, Humans, Italy, Middle Aged, Mitochondrial Proteins, Genetic Association Studies, Mutation, Genetic Association Studie, Disease, Settore MED/03 - GENETICA MEDICA, medicine.disease_cause, Exon, mental disorders, medicine, Mitochondrial Protein, Dementia, Neurology (clinical), Neuroscience (all), Developmental Biology, Geriatrics and Gerontology, Amyotrophic lateral sclerosi, business.industry, General Neuroscience, medicine.disease, 3. Good health, Cohort, Cohort Studie, business, Human, Frontotemporal dementia, Cohort study
Abstract: Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n= 64) and apparently sporadic ALS (n= 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ~1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs.
Published: 2015
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43. Nonradiative relaxation in thiophene-S,S-dioxide derivatives: The role of the environment

Author: Anni, M., Cingolani, R., Sala, F. Della, Gigli, G., Raganato, M.F., Barbarella, G., Fabiano, E., Favaretto, L., Lattante, S., and Gorling, A.
Subjects: Sulfur dioxide -- Research, Thiophene -- Chemical properties, Chemicals, plastics and rubber industries
Abstract: The intramolecular radiative and nonradiative relaxation processes of three thiophene-S,S-dioxide derivatives with different molecular rigidity are investigated in different solutions and inert matrix. It is shown that the fluorescence quantum efficiency and the relaxation dynamics are strongly dependent on the environment viscosity, whereas they are almost independent of the environment polarity.
Published: 2005

44. ATXN2 polyQ intermediate repeats are a modifier of ALS survival

Author: Chio', Adriano, Calvo, Andrea, Moglia, Cristina, Canosa, A., Brunetti, M., Barberis, M., Restagno, G., Conte, A., Bisogni, G., Marangi, G., Moncada, A., Lattante, S., Zollino, M., Sabatelli, M., Bagarotti, A., Corrado, L., Mora, G., Bersano, E., Mazzini, L., D'Alfonso, S., and Parals, F.
Subjects: Male, Oncology, medicine.medical_specialty, Population, Nerve Tissue Proteins, Cohort Studies, Internal medicine, medicine, Humans, Genetic Testing, Amyotrophic lateral sclerosis, education, Aged, Genetic testing, education.field_of_study, medicine.diagnostic_test, business.industry, Amyotrophic Lateral Sclerosis, Case-control study, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Ataxins, Italy, Case-Control Studies, Cohort, Female, Neurology (clinical), Peptides, business, Cohort study
Abstract: To analyze the frequency and clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) with intermediate-length (CAG) expansion (encoding 27-33 glutamines, polyQ) in the ATXN2 gene, in a population-based cohort of Italian patients with ALS (discovery cohort), and to replicate the findings in an independent cohort of consecutive patients from an ALS tertiary center (validation cohort).PolyQ repeats were assessed in 672 patients with incident ALS in Piemonte and Valle d'Aosta regions, Italy, in the 2007-2012 period (discovery cohort); controls were 509 neurologically healthy age- and sex-matched subjects resident in the study area. The validation cohort included 661 patients with ALS consecutively seen between 2001 and 2013 in the ALS Clinic Center of the Catholic University in Rome, Italy.In the discovery cohort, the frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (19 patients vs 1 control, p = 0.0001; odds ratio 14.8, 95% confidence interval 1.9-110.8). Patients with an increased number of polyQ repeats had a shorter survival than those with31 repeats (median survival, polyQ ≥31, 1.8 years, interquartile range [IQR] 1.3-2.2; polyQ31, 2.7 years, IQR 1.6-5.1; p = 0.001). An increased number of polyQ repeats remained independently significant at multivariable analysis. In the validation cohort, patients with ≥31 polyQ repeats had a shorter survival than those with31 repeats (median survival, polyQ ≥31, 2.0 years, IQR 1.5-3.4; polyQ31, 3.2 years, IQR 2.0-6.4; p = 0.007).ATXN2 polyQ intermediate-length repeat is a modifier of ALS survival. Disease-modifying therapies targeted to ATXN2 represent a promising therapeutic approach for ALS.
Published: 2015

45. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

Author: Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, Chiò A, Restagno G, Nicolaou N, Simon Sanchez J, van Swieten JC, Abramzon Y, Johnson JO, Sendtner M, Pamphlett R, Orrell RW, Mead S, Sidle KC, Houlden H, Rohrer JD, Morrison KE, Pall H, Talbot K, Ansorge O, Chromosome 9 ALS/FTD Consortium, French research network on FTLD/FTLD/ALS, ITALSGEN Consortium, Adamson G, Bayer AJ, Beck J, Callister JB, Blake DJ, Blumen SC, Collinge J, Dunckley T, Ealing J, East S, Elman L, Gerhard A, Guerreiro RJ, Gwinn K, Halliwell N, Hamdalla HH, Hewitt C, Ince P, Jablonka S, James C, Kent L, Knock JC, Lynch T, Mahoney C, Mann D, Neal J, Norris D, O'Dowd S, Richardson A, Rossor M, Rothstein J, Scholz SW, Snowden J, Stephan DA, Toulson G, Turner MR, Warren JD, Young K, Weng YH, Kuo HC, Lai SC, Huang CL, Camuzat A, Entraingues L, Guillot Noël, Verpillat P, Blanc F, Camu W, Clerget Darpoux F, Corcia P, Couratier P, Didic M, Dubois B, Duyckaerts C, Guedj E, Golfier V, Habert MO, Hannequin D, Lacomblez L, Meininger V, Salachas F, Levy R, Michel BF, Pasquier F, Puel M, Thomas Anterion C, Sellal F, Vercelletto M, Moglia C, Cammarosano S, Canosa A, Gallo S, Brunetti M, Ossola I, Marinou K, Papetti L, Pisano F, Pinter GL, Conte A, Luigetti M, Zollino M, Lattante S, Marangi G, la Bella V, Spataro R, Colletti T, Battistini S, Ricci C, Caponnetto C, Mancardi G, Mandich P, Salvi F, Bartolomei I, Mandrioli J, Sola P, Lunetta C, Penco S, Conforti FL, Gambardella A, Quattrone A, Volanti P, Floris G, Cannas A, Piras V, Marrosu F, Marrosu MG, Murru MR, Pugliatti M, Parish LD, Sotgiu A, Solinas G, Ulgheri L, Ticca A, Simone I, Logroscino G, Hernandez DG, Arepalli S, Sabatelli M, Mora G, Corbo M, Giannini F, Calvo A, Englund E, Borghero G, Floris GL, Remes AM, Laaksovirta H, McCluskey L, Trojanowski JQ, Van Deerlin VM, Schellenberg GD, Nalls MA, Drory VE, Lu CS, Yeh TH, Ishiura H, Takahashi Y, Tsuji S, Le Ber I, Brice A, Drepper C, Williams N, Kirby J, Shaw P, Hardy J, Tienari PJ, Heutink P, Morris HR, Pickering Brown S, Traynor BJ, MONSURRO', Maria Rosaria, TEDESCHI, Gioacchino, Majounie, E, Renton, Ae, Mok, K, Dopper, Eg, Waite, A, Rollinson, S, Chiò, A, Restagno, G, Nicolaou, N, Simon Sanchez, J, van Swieten, Jc, Abramzon, Y, Johnson, Jo, Sendtner, M, Pamphlett, R, Orrell, Rw, Mead, S, Sidle, Kc, Houlden, H, Rohrer, Jd, Morrison, Ke, Pall, H, Talbot, K, Ansorge, O, Chromosome, 9 ALS/FTD Consortium, French research network on, Ftld/ftld/al, Italsgen, Consortium, Adamson, G, Bayer, Aj, Beck, J, Callister, Jb, Blake, Dj, Blumen, Sc, Collinge, J, Dunckley, T, Ealing, J, East, S, Elman, L, Gerhard, A, Guerreiro, Rj, Gwinn, K, Halliwell, N, Hamdalla, Hh, Hewitt, C, Ince, P, Jablonka, S, James, C, Kent, L, Knock, Jc, Lynch, T, Mahoney, C, Mann, D, Neal, J, Norris, D, O'Dowd, S, Richardson, A, Rossor, M, Rothstein, J, Scholz, Sw, Snowden, J, Stephan, Da, Toulson, G, Turner, Mr, Warren, Jd, Young, K, Weng, Yh, Kuo, Hc, Lai, Sc, Huang, Cl, Camuzat, A, Entraingues, L, Guillot, Noël, Verpillat, P, Blanc, F, Camu, W, Clerget Darpoux, F, Corcia, P, Couratier, P, Didic, M, Dubois, B, Duyckaerts, C, Guedj, E, Golfier, V, Habert, Mo, Hannequin, D, Lacomblez, L, Meininger, V, Salachas, F, Levy, R, Michel, Bf, Pasquier, F, Puel, M, Thomas Anterion, C, Sellal, F, Vercelletto, M, Moglia, C, Cammarosano, S, Canosa, A, Gallo, S, Brunetti, M, Ossola, I, Marinou, K, Papetti, L, Pisano, F, Pinter, Gl, Conte, A, Luigetti, M, Zollino, M, Lattante, S, Marangi, G, la Bella, V, Spataro, R, Colletti, T, Battistini, S, Ricci, C, Caponnetto, C, Mancardi, G, Mandich, P, Salvi, F, Bartolomei, I, Mandrioli, J, Sola, P, Lunetta, C, Penco, S, Monsurro', Maria Rosaria, Tedeschi, Gioacchino, Conforti, Fl, Gambardella, A, Quattrone, A, Volanti, P, Floris, G, Cannas, A, Piras, V, Marrosu, F, Marrosu, Mg, Murru, Mr, Pugliatti, M, Parish, Ld, Sotgiu, A, Solinas, G, Ulgheri, L, Ticca, A, Simone, I, Logroscino, G, Hernandez, Dg, Arepalli, S, Sabatelli, M, Mora, G, Corbo, M, Giannini, F, Calvo, A, Englund, E, Borghero, G, Floris, Gl, Remes, Am, Laaksovirta, H, Mccluskey, L, Trojanowski, Jq, Van Deerlin, Vm, Schellenberg, Gd, Nalls, Ma, Drory, Ve, Lu, C, Yeh, Th, Ishiura, H, Takahashi, Y, Tsuji, S, Le Ber, I, Brice, A, Drepper, C, Williams, N, Kirby, J, Shaw, P, Hardy, J, Tienari, Pj, Heutink, P, Morris, Hr, Pickering Brown, S, and Traynor, Bj
Published: 2012

46. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, TREMOLIZZO, LUCIO, AROSIO, ALESSANDRO, FERRARESE, CARLO, Loi, D., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, TREMOLIZZO, LUCIO, AROSIO, ALESSANDRO, FERRARESE, CARLO, and Loi, D.
Abstract: There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients.
Published: 2016

47. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis

Author: Johnson, J. O., Pioro, E. P., Boehringer, A., Chia, R., Feit, H., Renton, A. E., Pliner, H. A., Abramzon, Y., Marangi, G., Winborn, B. J., Gibbs, J. R., Nalls, M. A., Morgan, S., Shoai, M., Hardy, J., Pittman, A., Orrell, R. W., Malaspina, A., Sidle, K. C., Fratta, P., Harms, M. B., Baloh, R. H., Pestronk, A., Weihl, C. C., Rogaeva, E., Zinman, L., Drory, V. E., Borghero, G., Mora, G., Calvo, A., Rothstein, J. D., Drepper, C., Sendtner, M., Singleton, A. B., Taylor, J. P., Cookson, M. R., Restagno, G., Sabatelli, M., Bowser, R., Chio`, A., Traynor, B. J., Moglia, C., Cammarosano, S., Canosa, A., Gallo, S., Brunetti, M., Ossola, I., Marinou, K., Papetti, L., Pisano, F., Pinter, G. L., Conte, A., Luigetti, M., Zollino, M., Lattante, S., la Bella, V., Spataro, R., Colletti, T., Battistini, S., Ricci, C., Caponnetto, C., Mancardi, G., Mandich, P., Salvi, F., Bartolomei, I., Mandrioli, J., Sola, P., Lunetta, C., Penco, S., Monsurro, M. R., Conforti, F. L., Tedeschi, G., Gambardella, A., Quattrone, A., Volanti, P., Floris, G., Cannas, A., Piras, V., Marrosu, F., Marrosu, M. G., Murru, M. R., Pugliatti, M., Parish, L. D., Sotgiu, A., Solinas, G., Ulgheri, L., Ticca, A., Simone, I., Logroscino, G., Pirisi, A., Johnson, JO, Pioro, EP, Boehringer, A, Chia, R, Feit, H5, Renton, AE, Pliner, HA, Abramzon, Y6, Marangi, G, Winborn, BJ, Gibbs, JR, Nalls, MA, Morgan, S, Shoai, M, Hardy, J, Pittman, A, Orrell, RW, Malaspina, A, Sidle, KC, Fratta, P, Harms, MB, Baloh, RH, Pestronk, A, Weihl, CC, Rogaeva, E, Zinman, L, Drory, VE, Borghero, G, Mora, G, Calvo, A, Rothstein, JD, ITALSGEN Consortium (including Cammarosano,S, Canosa, A, Moglia, C), Drepper, C, Sendtner, M, Singleton, AB, Taylor, JP, Cookson, MR, Restagno, G, Sabatelli, M, Bowser, R, Chiò, A, Traynor, BJ., Moglia, C., Canosa, A., Johnson, Jo, Pioro, Ep, Feit, H, Renton, Ae, Pliner, Ha, Abramzon, Y, Winborn, Bj, Gibbs, Jr, Nalls, Ma, Orrell, Rw, Sidle, Kc, Harms, Mb, Baloh, Rh, Weihl, Cc, Drory, Ve, Rothstein, Jd, Italsgen, Consortium, Among the, Collaborator, Monsurro', Maria Rosaria, Tedeschi, Gioacchino, Singleton, Ab, Taylor, Jp, Cookson, Mr, and Traynor, B. J.
Subjects: Male, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, genetics/pathology, Computational Biology, DNA Mutational Analysis, DNA-Binding Proteins, metabolism, Family Health, Female, Genetic Predisposition to Disease, genetics, Genotype, Humans, Male, Middle Aged, Muscle, Skeletal, metabolism/pathology, Mutation, genetics, Neurologic Examination, Nuclear Matrix-Associated Proteins, genetics/metabolism, RNA-Binding Proteins, genetics/metabolism, Spinal Cord, metabolism/pathology, DNA Mutational Analysis, genetics/metabolism, RNA-binding protein, Settore MED/03 - GENETICA MEDICA, medicine.disease_cause, 0302 clinical medicine, Nuclear Matrix-Associated Proteins, Genotype, 80 and over, genetics, Amyotrophic lateral sclerosis, Exome sequencing, Genetics, Aged, 80 and over, Neurologic Examination, 0303 health sciences, Mutation, General Neuroscience, RNA-Binding Proteins, Middle Aged, DNA-Binding Proteins, MATR3, medicine.anatomical_structure, Spinal Cord, familial amyotrophic lateral sclerosis, Muscle, Settore MED/26 - Neurologia, Female, Frontotemporal dementia, Article, 03 medical and health sciences, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Muscle, Skeletal, 030304 developmental biology, Aged, Family Health, business.industry, Amyotrophic Lateral Sclerosis, genetics/pathology, RNA, Computational Biology, Spinal cord, medicine.disease, genetic, business, Neuroscience, metabolism, 030217 neurology & neurosurgery
Abstract: MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. © 2014 Nature America, Inc. All rights reserved.
Published: 2014
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48. Erratum: Optical properties of N-succinimidyl bithiophene and the effects of the binding to biomolecules: Comparison between coupled-cluster and time-dependent density functional theory calculations and experiments (Journal Physical Chemistry B (2006) 110B (18651))

Author: Fabiano, E., Della Sala, F., Barbarella, G., Lattante, S., Anni, M., SOTGIU, Giovanna, Hättig, C., Cingolani, R., Gigli, G., Piacenza, M., Fabiano, E., Della Sala, F., Barbarella, G., Lattante, S., Anni, M., Sotgiu, Giovanna, Hättig, C., Cingolani, R., Gigli, G., and Piacenza, M.
Subjects: Materials Chemistry2506 Metals and Alloys, Surfaces, Coatings and Film, Physical and Theoretical Chemistry
Published: 2007

49. TBK1 is associated with ALS and ALS-FTD in Sardinian patients

Author: Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Occhineri, P, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Gibbs, J, Renton, A, Errichiello, E, Zoledziewska, M, Mulas, A, Qian, Y, Din, J, Pliner, H, Traynor, B, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mandich, P, Mancardi, G, Origone, P, Conforti, F, Vita, G, Messina, S, Russo, M, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Tremolizzo, L, Ferrarese, C, Fini, N, Fasano, A, Monsurrò, M, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Mazzini, L, D'Alfonso, S, Bersano, A, Corrado, L, Bagarotti, A, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Parish, L, Ortu, E, Ortu, E., TREMOLIZZO, LUCIO, FERRARESE, CARLO, Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Occhineri, P, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Gibbs, J, Renton, A, Errichiello, E, Zoledziewska, M, Mulas, A, Qian, Y, Din, J, Pliner, H, Traynor, B, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mandich, P, Mancardi, G, Origone, P, Conforti, F, Vita, G, Messina, S, Russo, M, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Tremolizzo, L, Ferrarese, C, Fini, N, Fasano, A, Monsurrò, M, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Mazzini, L, D'Alfonso, S, Bersano, A, Corrado, L, Bagarotti, A, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Parish, L, Ortu, E, Ortu, E., TREMOLIZZO, LUCIO, and FERRARESE, CARLO
Abstract: Recently, mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina). Genome analysis Toolkit was used to align and to code variants according to Human Genome (UCSC hg19). Mutation was confirmed with Sanger sequence. In our screening of 186 Sardinian ALS cases, we found 3 (1.6%) patients carrying 3 distinct novel genetic variants: a nonsynonymous SNV c.1150C>T leading to a p.Arg384Thr change in exon 9; a nonsynonymous SNV c.1331G>A causes a p.Arg444Gln change in exon 11; and a frameshift deletion c.2070delG (p.Met690fs) at the exon 20 of the gene leading to a stop at 693 codon. The latter patients also carried missense mutation c.98C>T of the SQSTM1 gene causing a substitution of an arginine with a valine at the position 33 (p.Arg33Val). All variants were found to be deleterious according to in silico predictions. All cases were apparently sporadic and one of them showed frontotemporal dementia associated to ALS. These mutations were not found in 2 cohorts of 6780 ethnic-matched controls. We have found that TBK1 mutations account for 1.6% of Sardinian ALS cases. Our data support the notion that TBK1 is a novel ALS gene, providing important evidence complementary to the first descriptions.
Published: 2015

50. ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

Author: Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Parish, L, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Renton, A, Nalls, M, Traynor, B, Restagno, G, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mancardi, G, Mandich, P, Origone, P, Conforti, F, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Nilo, R, Pinter, G, Corbo, M, Volanti, P, Mandrioli, J, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Monsurròad, M, Tedeschi, G, Cristillo, V, la Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Occhineri, P, Ortu, E, Logullo, FO, Conforti, FL, Pinter, GL, Monsurròad, MR, Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Parish, L, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Renton, A, Nalls, M, Traynor, B, Restagno, G, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mancardi, G, Mandich, P, Origone, P, Conforti, F, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Nilo, R, Pinter, G, Corbo, M, Volanti, P, Mandrioli, J, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Monsurròad, M, Tedeschi, G, Cristillo, V, la Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Occhineri, P, Ortu, E, Logullo, FO, Conforti, FL, Pinter, GL, and Monsurròad, MR
Abstract: Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival.
Published: 2015

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