118 results on '"Saletti V."'
Search Results
2. Progressive bone impairment with age and pubertal development in neurofibromatosis type I
- Author
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Rodari, Giulia, Scuvera, G., Ulivieri, F. M., Profka, E., Menni, F., Saletti, V., Esposito, S., Bergamaschi, S., Ferrante, E., Eller-Vainicher, C., Esposito, S., Arosio, M., and Giavoli, C.
- Published
- 2018
- Full Text
- View/download PDF
Catalog
3. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy
- Author
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Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., and Floridia S. more...
- Abstract
Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system. more...
- Published
- 2021
4. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy
- Author
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Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, and Floridia, S more...
- Subjects
Adult ,medicine.medical_specialty ,Telemedicine ,Neurology ,Referral ,Dermatology ,Telehealth ,03 medical and health sciences ,0302 clinical medicine ,Pandemic ,medicine ,Humans ,Outpatient clinic ,030212 general & internal medicine ,Medical prescription ,Child ,Pandemics ,Referral and Consultation ,SARS-CoV-2 ,business.industry ,Teleneurorehabilitation ,COVID-19 ,General Medicine ,medicine.disease ,Televisit ,Psychiatry and Mental health ,Italy ,Neuro-telehealth ,Neurology (clinical) ,Neurosurgery ,Medical emergency ,business ,030217 neurology & neurosurgery - Abstract
Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system. more...
- Published
- 2021
- Full Text
- View/download PDF
5. Vascular remodeling in moyamoya angiopathy: From peripheral blood mononuclear cells to endothelial cells
- Author
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Tinelli, F, Nava, S, Arioli, F, Bedini, G, Scelzo, E, Lisini, D, Faragò, G, Gioppo, A, Ciceri, E, Acerbi, F, Ferroli, P, Vetrano, I, Esposito, S, Saletti, V, Pantaleoni, C, Zibordi, F, Nardocci, N, Zedde, M, Pezzini, A, Lazzaro, V, Capone, F, Dell'Acqua, M, Vajkoczy, P, Tournier-Lasserve, E, Parati, E, Bersano, A, Gatti, L, Tinelli F., Nava S., Arioli F., Bedini G., Scelzo E., Lisini D., Faragò G., Gioppo A., Ciceri E. F., Acerbi F., Ferroli P., Vetrano I. G., Esposito S., Saletti V., Pantaleoni C., Zibordi F., Nardocci N., Zedde M. L., Pezzini A., Lazzaro V. D., Capone F., Dell'acqua M. L., Vajkoczy P., Tournier-Lasserve E., Parati E. A., Bersano A., Gatti L., Tinelli, F, Nava, S, Arioli, F, Bedini, G, Scelzo, E, Lisini, D, Faragò, G, Gioppo, A, Ciceri, E, Acerbi, F, Ferroli, P, Vetrano, I, Esposito, S, Saletti, V, Pantaleoni, C, Zibordi, F, Nardocci, N, Zedde, M, Pezzini, A, Lazzaro, V, Capone, F, Dell'Acqua, M, Vajkoczy, P, Tournier-Lasserve, E, Parati, E, Bersano, A, Gatti, L, Tinelli F., Nava S., Arioli F., Bedini G., Scelzo E., Lisini D., Faragò G., Gioppo A., Ciceri E. F., Acerbi F., Ferroli P., Vetrano I. G., Esposito S., Saletti V., Pantaleoni C., Zibordi F., Nardocci N., Zedde M. L., Pezzini A., Lazzaro V. D., Capone F., Dell'acqua M. L., Vajkoczy P., Tournier-Lasserve E., Parati E. A., Bersano A., and Gatti L. more...
- Abstract
The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology. more...
- Published
- 2020
6. Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients.
- Author
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Bianchessi, D, Ibba, M, Saletti, V, Blasa, S, Langella, T, Paterra, R, Cagnoli, G, Melloni, G, Scuvera, G, Natacci, F, Cesaretti, C, Finocchiaro, G, Eoli, M, Bianchessi D, Ibba MC, Saletti V, Blasa S, Langella T, Paterra R, Cagnoli GA, Melloni G, Scuvera G, Natacci F, Cesaretti C, Finocchiaro G, Eoli M, Bianchessi, D, Ibba, M, Saletti, V, Blasa, S, Langella, T, Paterra, R, Cagnoli, G, Melloni, G, Scuvera, G, Natacci, F, Cesaretti, C, Finocchiaro, G, Eoli, M, Bianchessi D, Ibba MC, Saletti V, Blasa S, Langella T, Paterra R, Cagnoli GA, Melloni G, Scuvera G, Natacci F, Cesaretti C, Finocchiaro G, and Eoli M more...
- Abstract
Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in NF1 gene; we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients; the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed; in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up. more...
- Published
- 2020
7. Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes
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Russo, S., Marchi, M., Cogliati, F., Bonati, M. T., Pintaudi, M., Veneselli, E., Saletti, V., Balestrini, M., Ben-Zeev, B., and Larizza, L.
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- 2009
- Full Text
- View/download PDF
8. Unilateral frontal lobe epilepsy affects executive functions in children
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Riva, D., Avanzini, G., Franceschetti, S., Nichelli, F., Saletti, V., Vago, C., Pantaleoni, C., D’Arrigo, S., Andreucci, E., Aggio, F., Paruta, N., and Bulgheroni, S.
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- 2005
- Full Text
- View/download PDF
9. Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1
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Koczkowska, M, Callens, T, Chen, Y, Gomes, A, Hicks, AD, Sharp, A, Johns, E, Uhas, KA, Armstrong, L, Bosanko, KA, Babovic-Vuksanovic, D, Baker, L, Basel, DG, Bengala, M, Bennett, JT, Chambers, C, Clarkson, LK, Clementi, M, Cortes, FM, Cunningham, M, D'Agostino, MD, Delatycki, MB, Digilio, MC, Dosa, L, Esposito, S, Fox, S, Freckmann, M-L, Fauth, C, Giugliano, T, Giustini, S, Goetsch, A, Goldberg, Y, Greenwood, RS, Griffis, C, Gripp, KW, Gupta, P, Haan, E, Hachen, RK, Haygarth, TL, Hernandez-Chico, C, Hodge, K, Hopkin, RJ, Hudgins, L, Janssens, S, Keller, K, Kelly-Mancuso, G, Kochhar, A, Korf, BR, Lewis, AM, Liebelt, J, Lichty, A, Listernick, RH, Lyons, MJ, Maystadt, I, Ojeda, MM, McDougall, C, McGregor, LK, Melis, D, Mendelsohn, N, Nowaczyk, MJM, Ortenberg, J, Panzer, K, Pappas, JG, Pierpont, ME, Piluso, G, Pinna, V, Pivnick, EK, Pond, DA, Powell, CM, Rogers, C, Shahar, NR, Rutledge, SL, Saletti, V, Sandaradura, SA, Santoro, C, Schatz, UA, Schreiber, A, Scott, DA, Sellars, EA, Sheffer, R, Siqveland, E, Slopis, JM, Smith, R, Spalice, A, Stockton, DW, Streff, H, Theos, A, Tomlinson, GE, Tran, G, Trapane, PL, Trevisson, E, Ullrich, NJ, Van den Ende, J, Vergano, SAS, Wallace, SE, Wangler, MF, Weaver, DD, Yohay, KH, Zackai, E, Zonana, J, Zurcher, V, Claes, KBM, Eoli, M, Martin, Y, Wimmer, K, De Luca, A, Legius, E, Messiaen, LM, Koczkowska, M, Callens, T, Chen, Y, Gomes, A, Hicks, AD, Sharp, A, Johns, E, Uhas, KA, Armstrong, L, Bosanko, KA, Babovic-Vuksanovic, D, Baker, L, Basel, DG, Bengala, M, Bennett, JT, Chambers, C, Clarkson, LK, Clementi, M, Cortes, FM, Cunningham, M, D'Agostino, MD, Delatycki, MB, Digilio, MC, Dosa, L, Esposito, S, Fox, S, Freckmann, M-L, Fauth, C, Giugliano, T, Giustini, S, Goetsch, A, Goldberg, Y, Greenwood, RS, Griffis, C, Gripp, KW, Gupta, P, Haan, E, Hachen, RK, Haygarth, TL, Hernandez-Chico, C, Hodge, K, Hopkin, RJ, Hudgins, L, Janssens, S, Keller, K, Kelly-Mancuso, G, Kochhar, A, Korf, BR, Lewis, AM, Liebelt, J, Lichty, A, Listernick, RH, Lyons, MJ, Maystadt, I, Ojeda, MM, McDougall, C, McGregor, LK, Melis, D, Mendelsohn, N, Nowaczyk, MJM, Ortenberg, J, Panzer, K, Pappas, JG, Pierpont, ME, Piluso, G, Pinna, V, Pivnick, EK, Pond, DA, Powell, CM, Rogers, C, Shahar, NR, Rutledge, SL, Saletti, V, Sandaradura, SA, Santoro, C, Schatz, UA, Schreiber, A, Scott, DA, Sellars, EA, Sheffer, R, Siqveland, E, Slopis, JM, Smith, R, Spalice, A, Stockton, DW, Streff, H, Theos, A, Tomlinson, GE, Tran, G, Trapane, PL, Trevisson, E, Ullrich, NJ, Van den Ende, J, Vergano, SAS, Wallace, SE, Wangler, MF, Weaver, DD, Yohay, KH, Zackai, E, Zonana, J, Zurcher, V, Claes, KBM, Eoli, M, Martin, Y, Wimmer, K, De Luca, A, Legius, E, and Messiaen, LM more...
- Abstract
We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p < .0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p < .0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population. more...
- Published
- 2020
10. Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation
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Koczkowska, M. (Magdalena), Callens, T. (Tom), Gomes, A. (Alicia), Sharp, A. (Angela), Chen, Y. (Yunjia), Hicks, A.D. (Alesha D.), Aylsworth, A.S. (Arthur S.), Azizi, A.A. (Amedeo A.), Basel, D.G. (Donald G.), Bellus, G. (Gary), Bird, L.M. (Lynne), Blazo, M. (Maria), Burke, L.W. (Leah W.), Cannon, A. (Ashley), Collins, F. (Felicity), DeFilippo, C. (Colette), Denayer, E. (Ellen), Digilio, M.C. (Maria), Dills, S.K. (Shelley K.), Dosa, L. (Laura), Greenwood, R.S. (Robert S.), Griffis, C. (Cristin), Gupta, P. (Punita), Hachen, R.K. (Rachel K.), Hernández-Chico, C. (Concepción), Janssens, S. (Sandra), Jones, K.J. (Kristi), Jordan, J.T. (Justin T.), Kannu, P. (Peter), Korf, B. (Bruce), Lewis, A.M. (Andrea M.), Listernick, R.H. (Robert H.), Lonardo, F. (Fortunato), Mahoney, M.J. (Maurice J.), Ojeda, M.M. (Mayra Martinez), McDougall, C. (Carey), Mendelsohn, N.J., Miller, D.T. (David T.), Mori, M. (Mari), Oostenbrink, R. (Rianne), Perreault, S. (Sebastien), Pierpont, M.E. (Mary Ella), Piscopo, C. (Carmelo), Pond, D.A. (Dinel A.), Randolph, L.M. (Linda M.), Rauen, K.A. (Katherine), Rednam, S. (Surya), Rutledge, S.L. (S. Lane), Saletti, V. (Veronica), Schaefer, G.B. (G. Bradley), Schorry, E.K. (Elizabeth K.), Scott, D.A., Shugar, A. (Andrea), Siqveland, E. (Elizabeth), Starr, L. (Lois), Syed, A. (Ashraf), Trapane, P.L. (Pamela L.), Ullrich, N.J. (Nicole J.), Wakefield, E.G. (Emily G.), Walsh, L.E. (Laurence E.), Wangler, M.F. (Michael F.), Zackai, E. (Elaine), Claes, K. (Kathleen), McDonald, M.T. (Marie), Wimmer, K. (Katharina), Thornton, A.S. (Andrew), De Luca, A. (Alessandro), Martin, Y. (Yolanda), Legius, E. (Eric), Messiaen, L.M. (Ludwine), Koczkowska, M. (Magdalena), Callens, T. (Tom), Gomes, A. (Alicia), Sharp, A. (Angela), Chen, Y. (Yunjia), Hicks, A.D. (Alesha D.), Aylsworth, A.S. (Arthur S.), Azizi, A.A. (Amedeo A.), Basel, D.G. (Donald G.), Bellus, G. (Gary), Bird, L.M. (Lynne), Blazo, M. (Maria), Burke, L.W. (Leah W.), Cannon, A. (Ashley), Collins, F. (Felicity), DeFilippo, C. (Colette), Denayer, E. (Ellen), Digilio, M.C. (Maria), Dills, S.K. (Shelley K.), Dosa, L. (Laura), Greenwood, R.S. (Robert S.), Griffis, C. (Cristin), Gupta, P. (Punita), Hachen, R.K. (Rachel K.), Hernández-Chico, C. (Concepción), Janssens, S. (Sandra), Jones, K.J. (Kristi), Jordan, J.T. (Justin T.), Kannu, P. (Peter), Korf, B. (Bruce), Lewis, A.M. (Andrea M.), Listernick, R.H. (Robert H.), Lonardo, F. (Fortunato), Mahoney, M.J. (Maurice J.), Ojeda, M.M. (Mayra Martinez), McDougall, C. (Carey), Mendelsohn, N.J., Miller, D.T. (David T.), Mori, M. (Mari), Oostenbrink, R. (Rianne), Perreault, S. (Sebastien), Pierpont, M.E. (Mary Ella), Piscopo, C. (Carmelo), Pond, D.A. (Dinel A.), Randolph, L.M. (Linda M.), Rauen, K.A. (Katherine), Rednam, S. (Surya), Rutledge, S.L. (S. Lane), Saletti, V. (Veronica), Schaefer, G.B. (G. Bradley), Schorry, E.K. (Elizabeth K.), Scott, D.A., Shugar, A. (Andrea), Siqveland, E. (Elizabeth), Starr, L. (Lois), Syed, A. (Ashraf), Trapane, P.L. (Pamela L.), Ullrich, N.J. (Nicole J.), Wakefield, E.G. (Emily G.), Walsh, L.E. (Laurence E.), Wangler, M.F. (Michael F.), Zackai, E. (Elaine), Claes, K. (Kathleen), McDonald, M.T. (Marie), Wimmer, K. (Katharina), Thornton, A.S. (Andrew), De Luca, A. (Alessandro), Martin, Y. (Yolanda), Legius, E. (Eric), and Messiaen, L.M. (Ludwine) more...
- Abstract
Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_2972 more...
- Published
- 2018
- Full Text
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11. The noncoding RNA AK127244 in 2p16.3 locus: A new susceptibility region for neuropsychiatric disorders
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Rizzo, A, Alfei, E, Zibordi, F, Saletti, V, Zorzi, G, Freri, E, Estienne, M, Girgenti, V, D'Arrigo, S, Esposito, S, Buldrini, B, Moroni, I, Milani, D, Granata, T, Ardissone, A, Eoli, M, Molteni, B, Bigoni, S, Pantaleoni, C, Nardocci, N, Sciacca, F, Rizzo, Ambra, Alfei, Enrico, Zibordi, Federica, Saletti, Veronica, Zorzi, Giovanna, Freri, Elena, Estienne, Margherita, Girgenti, Vita, D'Arrigo, Stefano, Esposito, Silvia, Buldrini, Barbara, Moroni, Isabella, Milani, Donatella, Granata, Tiziana, Ardissone, Anna, Eoli, Marica, Molteni, Bruna, Bigoni, Stefania, Pantaleoni, Chiara, Nardocci, Nardo, Sciacca, Francesca Luisa, Rizzo, A, Alfei, E, Zibordi, F, Saletti, V, Zorzi, G, Freri, E, Estienne, M, Girgenti, V, D'Arrigo, S, Esposito, S, Buldrini, B, Moroni, I, Milani, D, Granata, T, Ardissone, A, Eoli, M, Molteni, B, Bigoni, S, Pantaleoni, C, Nardocci, N, Sciacca, F, Rizzo, Ambra, Alfei, Enrico, Zibordi, Federica, Saletti, Veronica, Zorzi, Giovanna, Freri, Elena, Estienne, Margherita, Girgenti, Vita, D'Arrigo, Stefano, Esposito, Silvia, Buldrini, Barbara, Moroni, Isabella, Milani, Donatella, Granata, Tiziana, Ardissone, Anna, Eoli, Marica, Molteni, Bruna, Bigoni, Stefania, Pantaleoni, Chiara, Nardocci, Nardo, and Sciacca, Francesca Luisa more...
- Abstract
The presence of redundant copy number variants (CNVs) in groups of patients with neurological diseases suggests that these variants could have pathogenic effect. We have collected array comparative genomic hybridization (CGH) data of about 2,500 patients affected by neurocognitive disorders and we observed that CNVs in 2p16.3 locus were as frequent as those in 15q11.2, being both the most frequent unbalances in our cohort of patients. Focusing to 2p16.3 region, unbalances involving NRXN1 coding region have been already associated with neuropsychiatric disorders, although with incomplete penetrance, but little is known about CNVs located proximal to the gene, in the long noncoding RNA AK127244. We found that, in our cohort of patients with neuropsychiatric disorders, the frequency of CNVs involving AK127244 was comparable to that of NRXN1 gene. Patients carrying 2p16.3 unbalances shared some common clinical characteristics regardless NRXN1 and AK127244 CNVs localization, suggesting that the AK127244 long noncoding RNA could be involved in neurocognitive disease with the same effect of NRXN1 unbalances. AK127244 as well as NRXN1 unbalances seem to have a particular influence on language development, behavior or mood, according with the topographic correlation between NRXN1 expression and prefrontal cortex functions more...
- Published
- 2018
12. Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848
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Koczkowska, M, Chen, YJ (Yuan Jia), Callens, T, Gomes, A, Sharp, A, Johnson, S, Hsiao, MC, Chen, ZB, Balasubramanian, M, Barnett, CP, Becker, TA, Ben-Shachar, S, Bertola, DR, Blakeley, JO, Burkitt-Wright, EMM, Callaway, A, Crenshaw, M, Cunha, KS, Cunningham, M, D'Agostino, MD, Dahan, K, Luca, A, Destree, A, Dhamija, R, Eoli, M, Evans, DGR, Galvin-Parton, P, George-Abraham, JK, Gripp, KW, Guevara-Campos, J, Hanchard, NA, Hernandez-Chico, C, Immken, L, Janssens, S, Jones, KJ, Keena, BA, Kochhar, A, Liebelt, J, Martir-Negron, A, Mahoney, MJ, Maystadt, I, McDougall, C, McEntagart, M, Mendelsohn, N, Miller, DT, Mortier, G, Morton, J, Pappas, J, Plotkin, SR, Pond, D, Rosenbaum, K, Rubin, K, Russell, L, Rutledge, LS, Saletti, V, Schonberg, R, Schreiber, A, Seidel, M, Siqveland, E, Stockton, DW, Trevisson, E, Ullrich, NJ, Upadhyaya, M, van Minkelen, Rick, Verhelst, H, Wallace, MR, Yap, YS, Zackai, E, Zonana, J, Zurcher, V, Claes, K, Martin, Y, Korf, BR, Legius, E, Messiaen, LM, Koczkowska, M, Chen, YJ (Yuan Jia), Callens, T, Gomes, A, Sharp, A, Johnson, S, Hsiao, MC, Chen, ZB, Balasubramanian, M, Barnett, CP, Becker, TA, Ben-Shachar, S, Bertola, DR, Blakeley, JO, Burkitt-Wright, EMM, Callaway, A, Crenshaw, M, Cunha, KS, Cunningham, M, D'Agostino, MD, Dahan, K, Luca, A, Destree, A, Dhamija, R, Eoli, M, Evans, DGR, Galvin-Parton, P, George-Abraham, JK, Gripp, KW, Guevara-Campos, J, Hanchard, NA, Hernandez-Chico, C, Immken, L, Janssens, S, Jones, KJ, Keena, BA, Kochhar, A, Liebelt, J, Martir-Negron, A, Mahoney, MJ, Maystadt, I, McDougall, C, McEntagart, M, Mendelsohn, N, Miller, DT, Mortier, G, Morton, J, Pappas, J, Plotkin, SR, Pond, D, Rosenbaum, K, Rubin, K, Russell, L, Rutledge, LS, Saletti, V, Schonberg, R, Schreiber, A, Seidel, M, Siqveland, E, Stockton, DW, Trevisson, E, Ullrich, NJ, Upadhyaya, M, van Minkelen, Rick, Verhelst, H, Wallace, MR, Yap, YS, Zackai, E, Zonana, J, Zurcher, V, Claes, K, Martin, Y, Korf, BR, Legius, E, and Messiaen, LM more...
- Published
- 2018
13. A PDE10A de novo mutation causes childhood-onset chorea with diurnal fluctuations
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Esposito, S., Carecchio, M., Tonduti, D., Saletti, V., Panteghini, C., Chiapparini, L., Zorzi, G., Pantaleoni, C., Garavaglia, B., Krainc, D., Lubbe, S. J., Nardocci, N., and Mencacci, N. E.
- Subjects
Male ,Phosphoric Diester Hydrolases ,Chorea ,Mutation ,Brain ,Humans ,Child ,Preschool ,Chronobiology Disorders ,Child, Preschool ,Magnetic Resonance Imaging - Published
- 2017
14. Response to 'characteristics of 2p15-p16.1 microdeletion syndrome: review and description of two additional patients'
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Ronzoni, L., Saletti, V., Scuvera, G., Esposito, Susanna Maria Roberta, and Milani, D.
- Published
- 2015
15. NOVEL MUTATIONS IN CDKL5 GENE, PREDICTED EFFECTS AND ASSOCIATED PHENOTYPES
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Marchi, N., Guzzetti, S., Pintaudi, M., Cogliati, F., Gaggero, R., Saletti, V., Veneselli, EDVIGE MARIA, BEN ZEEV, B., Larizza, L., and Russo, S.
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- 2009
16. P14.01 * INTEGRATED GENETIC STUDIES OF NEUROFIBROMATOSIS TYPE 1. A TEN YEAR, ITALIAN EXPERIENCE
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Bianchessi, D., primary, Morosini, S., additional, Ibba, C., additional, Esposito, S., additional, Saletti, V., additional, Riva, D., additional, Natacci, F., additional, Finocchiaro, G., additional, and Eoli, M., additional more...
- Published
- 2014
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17. P.04.14 THE EVALUATION OF THE EFFICACY OF WEIGHT LOSS IN CONTROLLING SYMPTOMS IN PATIENTS WITH GASTROESOPHAGEAL REFLUX SYMPTOMS
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De Bortoli, N., primary, Guidi, G., additional, Saletti, V., additional, Martinucci, I., additional, Savarino, E., additional, Bertani, L., additional, Franchi, R., additional, Bellini, M., additional, Savarino, V., additional, and Marchi, S., additional more...
- Published
- 2013
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18. Intrathecal methotrexate affects cognitive function in children with medulloblastoma
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Riva, D., primary, Giorgi, C., additional, Nichelli, F., additional, Bulgheroni, S., additional, Massimino, M., additional, Cefalo, G., additional, Gandola, L., additional, Giannotta, M., additional, Bagnasco, I., additional, Saletti, V., additional, and Pantaleoni, C., additional more...
- Published
- 2002
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19. MRI features of cerebral lesions and cognitive functions in preterm spastic diplegic children
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Fedrizzi, E., Inverno, M., Grazia Bruzzone, M., Botteon, G., Saletti, V., and Farinotti, M.
- Abstract
The aim of this study is to further clarify the relation between the pattern of cognitive impairment in spastic diplegic children born preterm and MRI features of cerebral lesions. The cognitive profile by Wechsler Scale of a sample of 30 children aged 6 years, 8 months to 14 years, 7 months was assessed, and the correlations between the Full Scale, Verbal, and Performance IQ and periventricular leukomalacia features on MRI were investigated. A significant difference was observed between the mean Verbal and Performance IQ, indicating a specific failure in the visuoperceptual functions of spastic diplegic children born preterm. Periventricular leukomalacia was detected in all children. The severity of ventricular dilatation, the degree and extent of white matter reduction, optic radiation involvement, and the thinning of the posterior corpus callosum correlated significantly with the Full Scale and Performance IQ; no correlation was observed between the Verbal IQ and any of the MRI features analyzed. In spastic diplegic children, an MRI examination between the ages of 1 and 2 years may be helpful in predicting a specific neuropsychological pattern of dysfunction and in defining an early intervention program. more...
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- 1996
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20. NETWORK MEASUREMENT MODULE FOR EURONET IMPLEMENTED IN A MULTIMICROPROCESSOR ARRANGEMENT
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Faro, A., Messina, G., Mirabella, Orazio, and Saletti, V.
- Published
- 1981
21. Measurements on the Activity of the EIN Matching Unit (EMU)
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Alfonzetti, Salvatore, Casale, S, Faro, A, Saletti, V, and Scollo, Giuseppe
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- 1978
22. A Measurement System for the European Informatics Network Implemented on the Multi-microprocessor Interface with Euronet
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Alfonzetti, Salvatore, Casale, S, Faro, A, Saletti, V, and Scollo, Giuseppe
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- 1979
23. A network measurement module for Euronet implemented in a multimicrocomputer arrangment
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Faro, A, M. e. s. s. i. n. a. G., Mirabella, Orazio, and Saletti, V.
- Published
- 1981
24. Pitt-Hopkins syndrome: dissecting the clinical and genetic heterogeneity of conditions in the phenotypic spectrum
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Marangi, G., Frangella, S., Ricciardi, S., Chiurazzi, P., Orteschi, D., Lattante, S., Pettinato, R., Martinez, F., Magnani, C., Pantaleoni, C., Perria, C., Scarano, G., Saletti, V., Bonanni, P., Vasco, G., Lo Rizzo, C., Volzone, A., Alfei, E., Faletra, F., Romano, S., Renieri, A., Giannotta, M., Minetti, C., Bruno, C., Piccione, M., Stanzial, F., Della Monica, M., Ardissone, A., Di Giacomo, M., Agatino Battaglia, Graziano, C., Garavelli, L., and Zollino, M. more...
25. The phenotypic spectrum of neurodegeneration associated to PLA2G6 mutations
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Zorzi, G., Giovannetti, A., Zibordi, F., Saletti, V., Sessa, M., Orcesi, S., Morbin, M., Chiapparini, L., Barbara Garavaglia, and Nardocci, N.
26. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy (vol 47, pg 39, 2015)
- Author
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Muona, M., Berkovic, S. F., Dibbens, L. M., Karen Oliver, Maljevic, S., Bayly, M. A., Joensuu, T., Canafoglia, L., Franceschetti, S., Michelucci, R., Markkinen, S., Heron, S. E., Hildebrand, M. S., Andermann, E., Andermann, F., Gambardella, A., Tinuper, P., Licchetta, L., Scheffer, I. E., Criscuolo, C., Filla, A., Ferlazzo, E., Ahmad, J., Ahmad, A., Baykan, B., Said, E., Topcu, M., Riguzzi, P., King, M. D., Ozkara, C., Andrade, D. M., Engelsen, B. A., Crespel, A., Lindenau, M., Lohmann, E., Saletti, V., Massano, J., Privitera, M., Espay, A. J., Kauffmann, B., Duchowny, M., Moller, R. S., Straussberg, R., Afawi, Z., Ben-Zeev, B., Samocha, K. E., Daly, M. J., Petrou, S., Lerche, H., Palotie, A., and Lehesjoki, A. E. more...
27. Clinical and Molecular Spectrum of Myotonia and Periodic Paralyses Associated With Mutations in SCN4A in a Large Cohort of Italian Patients
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Lorenzo Maggi, Raffaella Brugnoni, Eleonora Canioni, Paola Tonin, Veronica Saletti, Patrizia Sola, Stefano Cotti Piccinelli, Lara Colleoni, Paola Ferrigno, Antonella Pini, Riccardo Masson, Fiore Manganelli, Daniele Lietti, Liliana Vercelli, Giulia Ricci, Claudio Bruno, Giorgio Tasca, Antonio Pizzuti, Alessandro Padovani, Carlo Fusco, Elena Pegoraro, Lucia Ruggiero, Sabrina Ravaglia, Gabriele Siciliano, Lucia Morandi, Raffaele Dubbioso, Tiziana Mongini, Massimiliano Filosto, Irene Tramacere, Renato Mantegazza, Pia Bernasconi, Maggi, L., Brugnoni, R., Canioni, E., Tonin, P., Saletti, V., Sola, P., Piccinelli, S. C., Colleoni, L., Ferrigno, P., Pini, A., Masson, R., Manganelli, F., Lietti, D., Vercelli, L., Ricci, G., Bruno, C., Tasca, G., Pizzuti, A., Padovani, A., Fusco, C., Pegoraro, E., Ruggiero, L., Ravaglia, S., Siciliano, G., Morandi, L., Dubbioso, R., Mongini, T., Filosto, M., Tramacere, I., Mantegazza, R., and Bernasconi, P. more...
- Subjects
0301 basic medicine ,periodic paralysis ,medicine.medical_specialty ,Weakness ,SCN4A gene mutation ,channelopathies ,myotonia ,SNEL ,voltage-gated sodium channel Na ,V ,1.4 ,Gastroenterology ,lcsh:RC346-429 ,voltage-gated sodium channel NaV1.4 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Paralysis ,Medicine ,Laryngospasm ,lcsh:Neurology. Diseases of the nervous system ,Original Research ,business.industry ,channelopathie ,Periodic paralysis ,Congenital myasthenic syndrome ,medicine.disease ,Myotonia ,Congenital myopathy ,030104 developmental biology ,Neurology ,Paramyotonia congenita ,Neurology (clinical) ,medicine.symptom ,business ,periodic paralysi ,030217 neurology & neurosurgery - Abstract
Background: Four main clinical phenotypes have been traditionally described in patients mutated in SCN4A, including sodium-channel myotonia (SCM), paramyotonia congenita (PMC), Hypokaliemic type II (HypoPP2), and Hyperkaliemic/Normokaliemic periodic paralysis (HyperPP/NormoPP); in addition, rare phenotypes associated with mutations in SCN4A are congenital myasthenic syndrome and congenital myopathy. However, only scarce data have been reported in literature on large patient cohorts including phenotypes characterized by myotonia and episodes of paralysis.Methods: We retrospectively investigated clinical and molecular features of 80 patients fulfilling the following criteria: (1) clinical and neurophysiological diagnosis of myotonia, or clinical diagnosis of PP, and (2) presence of a pathogenic SCN4A gene variant. Patients presenting at birth with episodic laryngospasm or congenital myopathy-like phenotype with later onset of myotonia were considered as neonatal SCN4A.Results: PMC was observed in 36 (45%) patients, SCM in 30 (37.5%), Hyper/NormoPP in 7 (8.7%), HypoPP2 in 3 (3.7%), and neonatal SCN4A in 4 (5%). The median age at onset was significantly earlier in PMC than in SCM (p < 0.01) and in Hyper/NormoPP than in HypoPP2 (p = 0.02). Cold-induced myotonia was more frequently observed in PMC (n = 34) than in SCM (n = 23) (p = 0.04). No significant difference was found in age at onset of episodes of paralysis among PMC and PP or in frequency of permanent weakness between PP (n = 4), SCM (n = 5), and PMC (n = 10). PP was more frequently associated with mutations in the S4 region of the NaV1.4 channel protein compared to SCM and PMC (p < 0.01); mutations causing PMC were concentrated in the C-terminal region of the protein, while SCM-associated mutations were detected in all the protein domains.Conclusions: Our data suggest that skeletal muscle channelopathies associated with mutations in SCN4A represent a continuum in the clinical spectrum. more...
- Published
- 2020
28. Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients
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Marica Eoli, Federica Natacci, Donatella Bianchessi, Tiziana Langella, Veronica Saletti, Claudia Cesaretti, Maria Cristina Ibba, Giulia Anna Cagnoli, Giulietta Scuvera, Stefania Blasa, Gaetano Finocchiaro, Giulia Melloni, Rosina Paterra, Bianchessi, D, Ibba, M, Saletti, V, Blasa, S, Langella, T, Paterra, R, Cagnoli, G, Melloni, G, Scuvera, G, Natacci, F, Cesaretti, C, Finocchiaro, G, and Eoli, M more...
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,MED/03 - GENETICA MEDICA ,lcsh:QH426-470 ,Genetic counseling ,030105 genetics & heredity ,Biology ,targeted next generation sequencing (NGS) ,neurofibromatosis type 1 ,DNA sequencing ,03 medical and health sciences ,symbols.namesake ,Genetics ,medicine ,Multiplex ,Multiplex ligation-dependent probe amplification ,Gene ,Genetics (clinical) ,Legius syndrome ,Sanger sequencing ,schwannomatosis ,neurofibromatosis type 1, targeted next generation sequencing (NGS), schwannomatosi ,Ion semiconductor sequencing ,medicine.disease ,nervous system diseases ,lcsh:Genetics ,030104 developmental biology ,symbols ,NF1, SPRED1, LZTR1, NF2 genes pathogenic variants - Abstract
Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in NF1 gene, we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients, the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed, in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up. more...
- Published
- 2020
29. The noncoding RNA AK127244 in 2p16.3 locus: A new susceptibility region for neuropsychiatric disorders
- Author
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Chiara Pantaleoni, Giovanna Zorzi, Vita Girgenti, Stefania Bigoni, Marica Eoli, Tiziana Granata, Margherita Estienne, Isabella Moroni, Francesca L. Sciacca, Veronica Saletti, Federica Zibordi, Stefano D'Arrigo, Elena Freri, Bruna Molteni, Nardo Nardocci, Enrico Alfei, Barbara Buldrini, Silvia Esposito, Donatella Milani, Anna Ardissone, Ambra Rizzo, Rizzo, A, Alfei, E, Zibordi, F, Saletti, V, Zorzi, G, Freri, E, Estienne, M, Girgenti, V, D'Arrigo, S, Esposito, S, Buldrini, B, Moroni, I, Milani, D, Granata, T, Ardissone, A, Eoli, M, Molteni, B, Bigoni, S, Pantaleoni, C, Nardocci, N, and Sciacca, F more...
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Adult ,Male ,0301 basic medicine ,RNA, Untranslated ,Adolescent ,DNA Copy Number Variations ,Cell Adhesion Molecules, Neuronal ,CNV ,Nerve Tissue Proteins ,Locus (genetics) ,Disease ,Biology ,Cohort Studies ,NRXN1 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Humans ,array CGH ,Coding region ,Genetic Predisposition to Disease ,long noncoding RNA ,Copy-number variation ,Child ,Neural Cell Adhesion Molecules ,Gene ,Genetics (clinical) ,Genetics ,Comparative Genomic Hybridization ,Mental Disorders ,Calcium-Binding Proteins ,Middle Aged ,Non-coding RNA ,Penetrance ,Psychiatry and Mental health ,Phenotype ,030104 developmental biology ,Case-Control Studies ,Child, Preschool ,Chromosomes, Human, Pair 2 ,Female ,RNA, Long Noncoding ,Comparative genomic hybridization - Abstract
The presence of redundant copy number variants (CNVs) in groups of patients with neurological diseases suggests that these variants could have pathogenic effect. We have collected array comparative genomic hybridization (CGH) data of about 2,500 patients affected by neurocognitive disorders and we observed that CNVs in 2p16.3 locus were as frequent as those in 15q11.2, being both the most frequent unbalances in our cohort of patients. Focusing to 2p16.3 region, unbalances involving NRXN1 coding region have been already associated with neuropsychiatric disorders, although with incomplete penetrance, but little is known about CNVs located proximal to the gene, in the long noncoding RNA AK127244. We found that, in our cohort of patients with neuropsychiatric disorders, the frequency of CNVs involving AK127244 was comparable to that of NRXN1 gene. Patients carrying 2p16.3 unbalances shared some common clinical characteristics regardless NRXN1 and AK127244 CNVs localization, suggesting that the AK127244 long noncoding RNA could be involved in neurocognitive disease with the same effect of NRXN1 unbalances. AK127244 as well as NRXN1 unbalances seem to have a particular influence on language development, behavior or mood, according with the topographic correlation between NRXN1 expression and prefrontal cortex functions. more...
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- 2018
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30. The molecular landscape of glioma in patients with Neurofibromatosis 1
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Dominique Vidaud, Mariona Suñol, Tala, Francesco DiMeco, John de Groot, Gaetano Finocchiaro, Fulvio D'Angelo, Luc Bauchet, Marica Eoli, Véronique Lorgis, David Meyronet, Kristin Alfaro, Luciano Garofano, John M. Slopis, Laurent Capelle, Pascale Varlet, Giulia Berzero, Mario Cangiano, Veronica Saletti, Romuald Seizeur, Jing Zhang, Carlo Efisio Marras, Veronique Frattini, Walid Farah, Cinzia Lavarino, David Cachia, Genevieve Lewis, Michele Ceccarelli, Seung-Ki Kim, David E. Reuss, Hugues Loiseau, Carlos Kamiya-Matsuoka, Do-Hyun Nam, Krishna P. Bhat, Stéphane Goutagny, Karima Mokhtari, François Ducray, Anna Lasorella, Colin Watts, Francesca Pia Caruso, Hector Salvador, Antonio Iavarone, F. Vandenbos, Ian E. McCutcheon, Susanna Ronchi, Viviane Tabar, Marc Sanson, D'Angelo, Fulvio, Ceccarelli, Michele, Tala, Garofano, Luciano, Zhang, Jing, Frattini, Veronique, Caruso, Francesca P., Lewis, Genevieve, Alfaro, Kristin D., Bauchet, Luc, Berzero, Giulia, Cachia, David, Cangiano, Mario, Capelle, Laurent, de Groot, John, Dimeco, Francesco, Ducray, Francoi, Farah, Walid, Finocchiaro, Gaetano, Goutagny, Stephane, Kamiya-Matsuoka, Carlo, Lavarino, Cinzia, Loiseau, Hugue, Lorgis, Veronique, Marras, Carlo E., Mccutcheon, Ian, Nam, Do-Hyun, Ronchi, Susanna, Saletti, Veronica, Seizeur, Romuald, Slopis, John, Sunol, Mariona, Vandenbos, Fanny, Varlet, Pascale, Vidaud, Dominique, Watts, Colin, Tabar, Viviane, Reuss, David E., Kim, Seung-Ki, Meyronet, David, Mokhtari, Karima, Salvador, Hector, Bhat, Krishna P., Eoli, Marica, Sanson, Marc, Lasorella, Anna, Iavarone, Antonio, D'Angelo, F., Ceccarelli, M., Garofano, L., Zhang, J., Frattini, V., Caruso, F. P., Lewis, G., Alfaro, K. D., Bauchet, L., Berzero, G., Cachia, D., Cangiano, M., Capelle, L., de Groot, J., Dimeco, F., Ducray, F., Farah, W., Finocchiaro, G., Goutagny, S., Kamiya-Matsuoka, C., Lavarino, C., Loiseau, H., Lorgis, V., Marras, C. E., Mccutcheon, I., Nam, D. -H., Ronchi, S., Saletti, V., Seizeur, R., Slopis, J., Sunol, M., Vandenbos, F., Varlet, P., Vidaud, D., Watts, C., Tabar, V., Reuss, D. E., Kim, S. -K., Meyronet, D., Mokhtari, K., Salvador, H., Bhat, K. P., Eoli, M., Sanson, M., Lasorella, A., Iavarone, A., Columbia University Medical Center (CUMC), Columbia University [New York], University of Sannio [Benevento], The University of Texas M.D. Anderson Cancer Center [Houston], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Medical University of South Carolina [Charleston] (MUSC), Service de Neurochirurgie [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), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Milan, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurochirurgie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Sungkyunkwan University [Suwon] (SKKU), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Pasteur [Nice] (CHU), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Sainte Anne [Paris], Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux (EA 7331), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], University of Birmingham [Birmingham], Memorial Sloane Kettering Cancer Center [New York], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), and CHU Cochin [AP-HP] more...
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0301 basic medicine ,Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,X-linked Nuclear Protein ,Neurofibromatosis 1 ,Adolescent ,[SDV]Life Sciences [q-bio] ,T-Lymphocytes ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Germline mutation ,CDKN2A ,Antigens, Neoplasm ,Glioma ,medicine ,Humans ,Epigenetics ,Neurofibromatosis ,10. No inequality ,Child ,Gene ,neoplasms ,ATRX ,Germ-Line Mutation ,Cancer ,Neurofibromin 1 ,Brain Neoplasms ,Reproducibility of Results ,General Medicine ,DNA Methylation ,Middle Aged ,medicine.disease ,3. Good health ,nervous system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Child, Preschool ,DNA methylation ,Cancer research ,Genomics, Bioinformatic ,Female ,Transcriptome - Abstract
Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic alterations of glioma that develops in NF1 patients and the similarities with sporadic glioma remain unknown. Here, we present the molecular landscape of low- and high-grade gliomas in patients affected by NF1 (NF1-glioma). We found that the predisposing germline mutation of the NF1 gene was frequently converted to homozygosity and the somatic mutational load of NF1-glioma was influenced by age and grade. High-grade tumors harbored genetic alterations of TP53 and CDKN2A, frequent mutations of ATRX associated with Alternative Lengthening of Telomere, and were enriched in genetic alterations of transcription/chromatin regulation and PI3 kinase pathways. Low-grade tumors exhibited fewer mutations that were over-represented in genes of the MAP kinase pathway. Approximately 50% of low-grade NF1-gliomas displayed an immune signature, T lymphocyte infiltrates, and increased neo-antigen load. DNA methylation assigned NF1-glioma to LGm6, a poorly defined Isocitrate Dehydrogenase 1 wild-type subgroup enriched with ATRX mutations. Thus, the profiling of NF1-glioma defined a distinct landscape that recapitulates a subset of sporadic tumors. An integrated analysis of glioma samples from patients with neurofibromatosis 1 annotates their mutational, epigenetic, transcriptional, and immunological features and uncovers similitudes with a subset of sporadic gliomas. more...
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- 2018
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31. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy
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Steven Petrou, Aarno Palotie, Danielle M. Andrade, Marta A. Bayly, Laura Licchetta, Ingrid E. Scheffer, Rikke S. Møller, Frederick Andermann, Laura Canafoglia, Arielle Crespel, Silvana Franceschetti, Veronica Saletti, Michael Duchowny, Michael S. Hildebrand, Ebba Lohmann, Antonio Gambardella, Eva Andermann, Chiara Criscuolo, Salla Markkinen, Bernt A. Engelsen, Cigdem Ozkara, Meral Topçu, Adeel Ahmad, Edoardo Ferlazzo, Holger Lerche, João Massano, Edith Said, Mary D. King, Paolo Tinuper, Alessandro Filla, Mikko Muona, Samuel F. Berkovic, Betül Baykan, Alberto J. Espay, Karen Oliver, Matthias Lindenau, Michael Privitera, Zaid Afawi, Tarja Joensuu, Leanne M. Dibbens, Bruria Ben-Zeev, Snezana Maljevic, Patrizia Riguzzi, Kaitlin E. Samocha, Birgit Kauffmann, Mark J. Daly, Roberto Michelucci, Rachel Straussberg, Sarah E. Heron, Anna-Elina Lehesjoki, Jamil Ahmad, Muona, Mikko, Berkovic, Samuel F, Dibbens, Leanne M, Oliver, Karen L, Bayly, Marta A, Heron, Sarah E, Lehesjoki, Anna-Elina, Muona, M., Berkovic, S.F., Dibbens, L.M., Oliver, K.L., Maljevic, S., Bayly, M.A., Joensuu, T., Canafoglia, L., Franceschetti, S., Michelucci, R., Markkinen, S., Heron, S.E., Hildebrand, M.S., Andermann, E., Andermann, F., Gambardella, A., Tinuper, P., Licchetta, L., Scheffer, I.E., Criscuolo, C., Filla, A., Ferlazzo, E., Ahmad, J., Ahmad, A., Baykan, B., Said, E., Topcu, M., Riguzzi, P., King, M.D., Ozkara, C., Andrade, D.M., Engelsen, B.A., Crespel, A., Lindenau, M., Lohmann, E., Saletti, V., Massano, J., Privitera, M., Espay, A.J., Kauffmann, B., Duchowny, M., Moller, R.S., Straussberg, R., Afawi, Z., Ben-Zeev, B., Samocha, K.E., Daly, M.J., Petrou, S., Lerche, H., Palotie, A., Lehesjoki, A.-E., Çocuk Sağlığı ve Hastalıkları, Maljevic, Snezana, Joensuu, Tarja, Canafoglia, Laura, Franceschetti, Silvana, Michelucci, Roberto, Markkinen, Salla, Hildebrand, Michael S, Andermann, Eva, Andermann, Frederick, Gambardella, Antonio, Tinuper, Paolo, Licchetta, Laura, Scheffer, Ingrid E, Criscuolo, Chiara, Filla, Alessandro, Ferlazzo, Edoardo, Ahmad, Jamil, Ahmad, Adeel, Baykan, Betul, Said, Edith, Topcu, Meral, Riguzzi, Patrizia, King, Mary D, Ozkara, Cigdem, Andrade, Danielle M, Engelsen, Bernt A, Crespel, Arielle, Lindenau, Matthia, Lohmann, Ebba, Saletti, Veronica, Massano, João, Privitera, Michael, Espay, Alberto J, Kauffmann, Birgit, Duchowny, Michael, Møller, Rikke S, Straussberg, Rachel, Afawi, Zaid, Ben Zeev, Bruria, Samocha, Kaitlin E, Daly, Mark J, Petrou, Steven, Lerche, Holger, Palotie, Aarno, and Lehesjoki, Anna Elina more...
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Male ,Protein Conformation ,PRNP protein, human ,SACS protein, human ,medicine.disease_cause ,genetics [Carrier Proteins] ,Epilepsy ,0302 clinical medicine ,genetics [Heat-Shock Proteins] ,Missense mutation ,Exome ,Conserved Sequence ,Heat-Shock Proteins ,Genes, Dominant ,Genetics & Heredity ,Genetics ,0303 health sciences ,Mutation ,GTPase-Activating Proteins ,Heat-Shock Protein ,genetics [Myoclonic Epilepsies, Progressive] ,KCNC1 protein, human ,3. Good health ,Pedigree ,Shaw Potassium Channels ,Prion ,Female ,medicine.symptom ,Human ,Ataxia ,Prions ,Molecular Sequence Data ,Mutation, Missense ,Nerve Tissue Proteins ,Progressive myoclonus epilepsy ,Biology ,Article ,Prion Proteins ,03 medical and health sciences ,Species Specificity ,physiology [Shaw Potassium Channels] ,ddc:570 ,medicine ,Animals ,Humans ,Point Mutation ,Shaw Potassium Channel ,Amino Acid Sequence ,030304 developmental biology ,genetics [Shaw Potassium Channels] ,Base Sequence ,Sequence Homology, Amino Acid ,Animal ,genetics [Prions] ,Point mutation ,Membrane Proteins ,medicine.disease ,Myoclonic Epilepsies, Progressive ,Molecular biology ,SHAKER K+ CHANNEL DNA-SEQUENCING DATA ATAXIA TYPE 13 POTASSIUM CHANNEL S4 SEGMENT CYSTATIN-B DISEASE FREQUENCY FRAMEWORK ONSET ,Amino Acid Substitution ,KCNC1 ,epilepsy ,TBC1D24 protein, human ,mutation ,Carrier Protein ,Carrier Proteins ,Myoclonus ,Sequence Alignment ,030217 neurology & neurosurgery - Abstract
Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31 %). Remarkably, a recurrent de novo mutation, c. 959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity. Refereed/Peer-reviewed more...
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- 2015
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32. Which type of duraplasty is best for Chiari type I malformation surgery?
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Valentini LG, Saletti V, Moscatelli M, Ferrari E, Farinotti M, Barbotti A, Vetrano IG, and Galbiati TF
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- Humans, Male, Female, Retrospective Studies, Adult, Child, Middle Aged, Adolescent, Decompression, Surgical methods, Young Adult, Cerebrospinal Fluid Leak surgery, Cerebrospinal Fluid Leak epidemiology, Postoperative Complications epidemiology, Child, Preschool, Animals, Treatment Outcome, Arnold-Chiari Malformation surgery, Dura Mater surgery
- Abstract
Objective: This study investigated whether the selection of different dural substitutes and distinct dural repair techniques correlates with the incidence rate of postoperative CSF leak in a mixed population of adults and children with Chiari type I malformation (CM-I) who underwent posterior fossa decompression with enlargement duraplasty (PFDD) as the first surgical approach., Methods: A retrospective analysis was conducted on all patients admitted to the authors' institution between 2006 and 2023 for PFDD to treat syringomyelia and/or symptoms due to CM-I. Clinical, radiological, and surgical data were extracted from a prospectively maintained database. Demographic information was collected from medical records. Surgical procedures were also scrutinized, specifically focusing on the type of dural graft used for duraplasty, alongside perioperative complications and the necessity for subsequent surgeries. Lastly, during follow-up, the occurrence of a CSF leak was assessed and analyzed in relation to the type of dural graft used during surgery. The type of dural substitute chosen changed over the years to reduce CSF fistulas, while the technique of PFDD remained the same. Consequently, large sequential homogeneous groups differing only by dural substitutes were available for comparison., Results: The data from 409 patients with CM-I undergoing PFDD were analyzed. A total of 368 cases had complete surgical data and were included. Thirty patients received autologous duraplasty. The remaining 338 cases with heterologous duraplasty from equine and bovine pericardium were considered for the comparative statistical analysis. The mean follow-up duration ranged from 39 months in adults to 45 months in children. The CSF complication rate requiring revision was 6.5% in the total cohort, with a higher incidence in children (10.5%) compared with adults (3.9%). There was no significant difference in adverse events (CSF leak, revision surgery, or ventriculoperitoneal shunt placement) between the different dural patches by univariate analysis if applied to the total cohort, although the trend neared significance (p = 0.06). In pediatric cases, this value was significant (p = 0.01) in favor of equine pericardium, particularly when combined with a collagen matrix inlay graft., Conclusions: This study on a large and homogeneous series of patients with CM-I undergoing PFDD with heterologous duraplasty demonstrated that CSF complications may be kept low. The dural substitutes derived from equine pericardium, particularly when combined with a collagen matrix inlay graft, exhibited a reduced rate of CSF leaks compared with substitutes derived from bovine pericardium. more...
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- 2025
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33. Quality of life, functioning and participation of children and adolescents with visual impairment: A scoping review.
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Lanza M, Incagli F, Ceccato C, Reffo ME, Mercuriali E, Parmeggiani F, Pagliano E, Saletti V, Leonardi M, Suppiej A, Dollfus H, LeBreton D, Finger RP, Leroy BP, Zemaitiene R, Nowomiejska K, and Guastafierro E more...
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- Humans, Child, Adolescent, Social Participation psychology, Child, Preschool, Quality of Life psychology, Vision Disorders psychology
- Abstract
Background: Vision has a key role in children's neuromotor, cognitive and social development. Children with visual impairment attain developmental milestones at later stages and are at higher risk of developing psychological disorders and social withdrawn., Aims: We performed a scoping review to summarize the mostly used instruments assessing the impact of visual impairment on quality of life, functioning and participation of children and adolescents. In addition, the main findings of the included studies are discussed., Methods and Procedures: We searched for papers assessing quality of life, functioning and participation of children and adolescents with visual impairment from 0 to 18 years old conducted between 2000 and 2023., Outcomes and Results: In total, 69 studies met the inclusion criteria and were included in the review. Child self-report, caregivers-proxy and self-report questionnaires as well as interviews were used. The results showed that quality of life, functioning and participation are significantly reduced in children and adolescents with visual impairment, and that the impact depends on different factors (e.g., severity of the impairment, age)., Conclusions and Implications: Considering the significant impact of visual impairment on quality of life, functioning and participation on this population, it is fundamental to develop integrated and multi-dimensional assessment programs that evaluate the impact of visual impairment on those dimensions considering different contexts of life (e.g., family, school, leisure time). WHAT THIS PAPER ADDS?: The present review aims to give an overview of what is known about the impact of visual impairment on quality of life, functioning and participation of children and adolescents. We assumed a biopsychosocial perspective which, in line with the definition of health by the International Classification of Functioning, Disability and Health (WHO, 2001), considered how body functions and structures, functioning, participation and environmental factors dynamically interact to define the health, or the disease, status of a person at a certain moment of life. We reported the most used instruments for the assessment of quality of life, participation, and functioning, with a specific interest on Patient-Reported Outcome Measures and self-report measures. By reporting the different instruments used, we gave a broad overview about the available tools that can be used in clinical as well as in research field to assess quality of life, functioning and participation in this population. Additionally, the review of the existing literature allowed us to demonstrate that those dimensions are negatively impacted by visual impairment and thus they should be considered in the assessment programs. Specifically, there is the need to provide more integrated assessment programs that investigate the impact of visual impairment on children and adolescents' social and emotional wellbeing, everyday functioning and social relationship, considering their subjective experience together with the one of caregivers, teachers, health care professionals, and other relevant adults involved in their life. Additionally, it is essential to plan and implement multidimensional assessment programs that consider how all areas of life are differently impacted by visual impairment., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...
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- 2024
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34. Cognitive, Neuropsychological and Biological Effects of Oxygen-Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial.
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Scassellati C, Bonvicini C, Ciani M, Zanardini R, Tomasoni E, Saletti V, Passeggia I, Almici M, Pagnoni I, Galoforo AC, Costa M, D'Onofrio M, Cattaneo A, and Geroldi C
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Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world's population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O
3 ) in a cohort of subjects stratified according to CF scores. We also studied the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons were recruited and randomly assigned to receive the active treatment (150 cc of oxygen-O2 -O3 mixture at the concentration of 30 µg of O3 per cc of O2 ), O2 , or the placebo (air) for 5 weeks. The main endpoints were the change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), and 15 (T15) after treatment and the change in biomarker levels resulting from transcriptomics, proteomics, and metabolomic patterns at the same times. The positive results from this study could have important clinical implications. more...- Published
- 2024
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35. Genetic/epigenetic effects in NF1 microdeletion syndrome: beyond the haploinsufficiency, looking at the contribution of not deleted genes.
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Tritto V, Bettinaglio P, Mangano E, Cesaretti C, Marasca F, Castronovo C, Bordoni R, Battaglia C, Saletti V, Ranzani V, Bodega B, Eoli M, Natacci F, and Riva P
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- Humans, Female, Male, Neurofibromin 1 genetics, Chromosomes, Human, Pair 17 genetics, Phenotype, Child, Promoter Regions, Genetic, Haploinsufficiency, Neurofibromatosis 1 genetics, Epigenesis, Genetic, Chromosome Deletion
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NF1 microdeletion syndrome, accounting for 5-11% of NF1 patients, is caused by a deletion in the NF1 region and it is generally characterized by a severe phenotype. Although 70% of NF1 microdeletion patients presents the same 1.4 Mb type-I deletion, some patients may show additional clinical features. Therefore, the contribution of several pathogenic mechanisms, besides haploinsufficiency of some genes within the deletion interval, is expected and needs to be defined. We investigated an altered expression of deletion flanking genes by qPCR in patients with type-1 NF1 deletion, compared to healthy donors, possibly contributing to the clinical traits of NF1 microdeletion syndrome. In addition, the 1.4-Mb deletion leads to changes in the 3D chromatin structure in the 17q11.2 region. Specifically, this deletion alters DNA-DNA interactions in the regions flanking the breakpoints, as demonstrated by our 4C-seq analysis. This alteration likely causes position effect on the expression of deletion flanking genes.Interestingly, 4C-seq analysis revealed that in microdeletion patients, an interaction was established between the RHOT1 promoter and the SLC6A4 gene, which showed increased expression. We performed NGS on putative modifier genes, and identified two "likely pathogenic" rare variants in RAS pathway, possibly contributing to incidental phenotypic features.This study provides new insights into understanding the pathogenesis of NF1 microdeletion syndrome and suggests a novel pathomechanism that contributes to the expression phenotype in addition to haploinsufficiency of genes located within the deletion.This is a pivotal approach that can be applied to unravel microdeletion syndromes, improving precision medicine, prognosis and patients' follow-up., (© 2024. The Author(s).) more...
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- 2024
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36. Feasibility and usability of remote monitoring in Alzheimer's disease.
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Muurling M, de Boer C, Hinds C, Atreya A, Doherty A, Alepopoulos V, Curcic J, Brem AK, Conde P, Kuruppu S, Morató X, Saletti V, Galluzzi S, Vilarino Luis E, Cardoso S, Stukelj T, Kramberger MG, Roik D, Koychev I, Hopøy AC, Schwertner E, Gkioka M, Aarsland D, and Visser PJ more...
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Introduction: Remote monitoring technologies (RMTs) can measure cognitive and functional decline objectively at-home, and offer opportunities to measure passively and continuously, possibly improving sensitivity and reducing participant burden in clinical trials. However, there is skepticism that age and cognitive or functional impairment may render participants unable or unwilling to comply with complex RMT protocols. We therefore assessed the feasibility and usability of a complex RMT protocol in all syndromic stages of Alzheimer's disease and in healthy control participants., Methods: For 8 weeks, participants (N = 229) used two activity trackers, two interactive apps with either daily or weekly cognitive tasks, and optionally a wearable camera. A subset of participants participated in a 4-week sub-study (N = 45) using fixed at-home sensors, a wearable EEG sleep headband and a driving performance device. Feasibility was assessed by evaluating compliance and drop-out rates. Usability was assessed by problem rates (e.g., understanding instructions, discomfort, forgetting to use the RMT or technical problems) as discussed during bi-weekly semi-structured interviews., Results: Most problems were found for the active apps and EEG sleep headband. Problem rates increased and compliance rates decreased with disease severity, but the study remained feasible., Conclusions: This study shows that a highly complex RMT protocol is feasible, even in a mild-to-moderate AD population, encouraging other researchers to use RMTs in their study designs. We recommend evaluating the design of individual devices carefully before finalizing study protocols, considering RMTs which allow for real-time compliance monitoring, and engaging the partners of study participants in the research., Competing Interests: JC is an employee and shareholder of Novartis. AD is supported by the Welcome Trust [223100/Z/21/Z]. Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam. DA has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals, Biogen, and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Mentis Cura, and Roche Diagnostics. IK declares support for this work through the National Institute of Health Research (personal award and Oxford Health Biomedical Research Centre) and the Medical Research Council (Dementias Platform UK grant), and is a paid medical advisor for digital healthcare technology companies (Five Lives SAS and Cognetivity Ltd). All other authors declare that there is no conflict of interest., (© The Author(s) 2024.) more...
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- 2024
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37. Surgical Management of Chiari 1.5 in Children: A Truly Different Disease?
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Vetrano IG, Barbotti A, Galbiati TF, Mariani S, Erbetta A, Chiapparini L, Saletti V, and Valentini LG
- Abstract
Background: In patients with Chiari 1.5 malformation (CM1.5), a more aggressive disease course and an increased association with craniovertebral junction (CVJ) anomalies has been suggested. The best management of this subgroup of patients is not clearly defined, also due to the lack of specific series elucidating this anomaly's peculiar characteristics. Methods: We evaluated a series of 33 patients (25 females, 8 males; mean age at surgery: 13 years) fulfilling the criteria for Chiari 1.5 diagnosis who underwent posterior fossa decompression and duraplasty (PFDD) between 2006 and 2021. Results: Headache was present in all children, five presented central apnea, five had dysphagia, and three had rhinolalia. Syringomyelia was present in 19 (58%) children. Twenty patients (61%) showed various CVJ anomalies, but only one child presented instability requiring arthrodesis. The mean tonsil displacement below the foramen magnum was 19.9 mm (range: 12-30), without significant correlation with the severity of symptoms. Syringomyelia recurred or was unchanged in three patients, and one needed C1-C2 fixation. The headache disappeared in 28 children (84%). Arachnoid opening and tonsil coagulation or resection was necessary for 19 children (58%). Conclusions: In our pediatric CM series, the need for tonsil resection or coagulation was higher in CM1.5 children due to a more severe crowding. more...
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- 2024
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38. New insights into the molecular basis of spinal neurofibromatosis type 1.
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Bettinaglio P, Mangano E, Tritto V, Bordoni R, Paterra R, Borghi A, Volontè M, Battaglia C, Saletti V, Cesaretti C, Natacci F, Melone MAB, Eoli M, and Riva P
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- Humans, Neurofibromin 1 genetics, Mutation, Syndecans genetics, Genes, Neurofibromatosis 1, Neurofibromatosis 1 genetics, Neurofibromatoses
- Abstract
Spinal neurofibromatosis (SNF) is a form of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas involving all spinal roots. The pathogenic mechanisms determining the SNF form are currently unknown. To verify the presence of genetic variants possibly related to SNF or classic NF1, we studied 106 sporadic NF1 and 75 SNF patients using an NGS panel of 286 genes encoding RAS pathway effectors and neurofibromin interactors and evaluated the expression of syndecans (SDC1, SDC2, SDC3, SDC4), the NF1 3' tertile interactors, by quantitative real-time PCR. We previously identified 75 and 106 NF1 variants in SNF and NF1 cohorts, respectively. The analysis of the distribution of pathogenic NF1 variants in the three NF1 tertiles showed a significantly higher prevalence of NF1 3' tertile mutations in SNF than in the NF1 cohort. We hypothesized a potential pathogenic significance of the 3' tertile NF1 variants in SNF. The analysis of syndecan expression on PBMCs RNAs from 16 SNF, 16 classic NF1 patients and 16 healthy controls showed that the expression levels of SDC2 and SDC3 were higher in SNF and NF1 patients than in controls; moreover, SDC2, SDC3 and SDC4 were significantly over expressed in patients mutated in the 3' tertile compared to controls. Two different mutational NF1 spectra seem to characterize SNF and classic NF1, suggesting a pathogenic role of NF1 3' tertile and its interactors, syndecans, in SNF. Our study, providing new insights on a possible role of neurofibromin C-terminal in SNF, could address effective personalized patient management and treatments., (© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.) more...
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- 2023
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39. Case report: SLC6A1 mutations presenting with isolated absence seizures: description of 2 novel cases.
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Caputo D, Franceschetti S, Castellotti B, Freri E, Zorzi G, Saletti V, Canafoglia L, and Granata T
- Abstract
We report the clinical and EEG data of two patients harboring heterozygous SLC6A1 mutations, who presented with typical absence seizures at 3 Hz spike and wave as well as with mild cognitive disability. Neuroradiological and other laboratory investigations were normal. Our observations suggest that SLC6A1 mutations can be suspected in children with typical absences as the only seizure type, especially if associated with, even mild, cognitive deficits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Caputo, Franceschetti, Castellotti, Freri, Zorzi, Saletti, Canafoglia and Granata.) more...
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- 2023
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40. Cognitive and Behavioral Outcome of Pediatric Low-Grade Central Nervous System Tumors Treated Only with Surgery: A Single Center Experience.
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Taddei M, Esposito S, Marucci G, Erbetta A, Ferroli P, Valentini LG, Pantaleoni C, D'Arrigo S, Saletti V, Pollo B, Paterra R, Riva D, and Bulgheroni S
- Abstract
Background: The present mono-institutional report aimed to describe the cognitive and behavioral outcomes of low-grade central nervous system (CNS) tumors in a cohort of children treated exclusively with surgical intervention., Methods: Medical records from 2000-2020 were retrospectively analyzed. We included 38 children (mean age at first evaluation 8 years and 3 months, 16 females) who had undergone presurgical cognitive-behavioral evaluation and/or at least 6 months follow-up. Exclusion criteria were a history of traumatic brain injury, stroke, cerebral palsy or cancer-predisposing syndromes., Results: The sample presented cognitive abilities and behavioral functioning in the normal range, with weaknesses in verbal working memory and processing speed. The obtained results suggest that cognitive and behavioral functioning is related to pre-treatment variables (younger age at symptoms' onset, glioneuronal histological type, cortical location with preoperative seizures), timing of surgery and seizure control after surgery, and is stable when controlling for a preoperative cognitive and behavioral baseline. Younger age at onset is confirmed as a particular vulnerability in determining cognitive sequelae, and children at older ages or at longer postsurgical follow-up are at higher risk for developing behavioral disturbances., Conclusions: Timely treatment is an important factor influencing the global outcome and daily functioning of the patients. Preoperative and regular postsurgical cognitive and behavioral assessment, also several years after surgery, should be included in standard clinical practices. more...
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- 2023
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41. Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.
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Mussa A, Leoni C, Iacoviello M, Carli D, Ranieri C, Pantaleo A, Buonuomo PS, Bagnulo R, Ferrero GB, Bartuli A, Melis D, Maitz S, Loconte DC, Turchiano A, Piglionica M, De Luisi A, Susca FC, Bukvic N, Forleo C, Selicorni A, Zampino G, Onesimo R, Cappuccio G, Garavelli L, Novelli C, Memo L, Morando C, Della Monica M, Accadia M, Capurso M, Piscopo C, Cereda A, Di Giacomo MC, Saletti V, Spinelli AM, Lastella P, Tenconi R, Dvorakova V, Irvine AD, and Resta N more...
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- Humans, Mutation genetics, Phenotype, Genotype, Class I Phosphatidylinositol 3-Kinases genetics, p120 GTPase Activating Protein genetics, Vascular Malformations diagnosis, Vascular Malformations genetics
- Abstract
Background: Postzygotic activating PIK3CA variants cause several phenotypes within the PIK3CA -related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007 PIK3CA- mutated patients, analysing our new data with previous literature to give a comprehensive picture., Methods: We performed ultradeep targeted next-generation sequencing (NGS) on DNA from skin biopsy, buccal swab or blood using a panel including phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway genes and GNAQ , GNA11 , RASA1 and TEK . Additionally, 914 patients previously reported were systematically reviewed., Results: 93 of our 150 patients had PIK3CA pathogenetic variants. The merged PROS cohort showed that PIK3CA variants span thorough all gene domains, some were exclusively associated with specific PROS phenotypes: weakly activating variants were associated with central nervous system (CNS) involvement, and strongly activating variants with extra-CNS phenotypes. Among the 57 with a wild-type PIK3CA allele, 11 patients with overgrowth and vascular malformations overlapping PROS had variants in GNAQ , GNA11 , RASA1 or TEK ., Conclusion: We confirm that (1) molecular diagnostic yield increases when multiple tissues are tested and by enriching NGS panels with genes of overlapping 'vascular' phenotypes; (2) strongly activating PIK3CA variants are found in affected tissue, rarely in blood: conversely, weakly activating mutations more common in blood; (3) weakly activating variants correlate with CNS involvement, strong variants are more common in cases without; (4) patients with vascular malformations overlapping those of PROS can harbour variants in genes other than PIK3CA ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.) more...
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- 2023
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42. CGH Findings in Children with Complex and Essential Autistic Spectrum Disorder.
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Annunziata S, Bulgheroni S, D'Arrigo S, Esposito S, Taddei M, Saletti V, Alfei E, Sciacca FL, Rizzo A, Pantaleoni C, and Riva D
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- Humans, Child, Comparative Genomic Hybridization methods, DNA Copy Number Variations genetics, Cognition, Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder genetics, Child Development Disorders, Pervasive
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Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a strong genetic basis. We accurately assessed 209 ASD subjects, categorized in complex (47) and essential (162), and performed array comparative genomic hybridization to identify pathogenic and recurrent Copy Number Variants (CNVs). We found 117 CNVs in 75 patients, 11 classified as pathogenic. The complex ASD subjects have higher frequency of pathogenic CNVs with a diagnostic yield of 12.8%. Familiality, cognitive and verbal abilities, severity of autistic symptoms, neuroimaging and neurophysiological findings are not related to genetic data. This study identifies loci of interest for ASD and highlights the importance of a careful phenotypic characterization, as complex ASD is related to higher rate of pathogenic CNVs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.) more...
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- 2023
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43. Increase of Circulating Endothelial Progenitor Cells and Released Angiogenic Factors in Children with Moyamoya Arteriopathy.
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Gorla G, Carrozzini T, Pollaci G, Potenza A, Nava S, Acerbi F, Ferroli P, Esposito S, Saletti V, Ciusani E, Zulueta A, Parati EA, Bersano A, Gatti L, and Vetrano IG
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- Humans, Child, Endothelial Progenitor Cells pathology, Moyamoya Disease pathology, Hemorrhagic Stroke
- Abstract
Moyamoya arteriopathy (MMA) is a rare cerebrovascular disorder that causes recurrent ischemic and hemorrhagic strokes, leading young patients to severe neurological deficits. The pathogenesis of MMA is still unknown. The disease onset in a wide number of pediatric cases raises the question of the role of genetic factors in the disease's pathogenesis. In these patients, MMA's clinical course, or progression, is largely unclear. By performing a comprehensive molecular and cellular profile in the plasma and CSF, respectively, of MMA pediatric patients, our study is aimed at assessing the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins at an early disease stage to clarify MMA pathogenesis and progression. We employed cytofluorimetric methods and immunoassays in pediatric MMA patients and matched control subjects by age and sex. We detected increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF (i.e., angiopoietin-2 and VEGF-A). This finding is probably associated with deregulated angiogenesis, as stated by the moderate severity of collateral vessel network development (Suzuki III-IV). The absence of significant modulation of neurofilament light in CSF led us to rule out the presence of substantial neuronal injury in MMA children. Despite the limited cohort of pediatric patients, we found some peculiar cellular and molecular characteristics in their blood and CSF samples. Our findings may be confirmed by wider and perspective studies to identify predictive or prognostic circulating biomarkers and potential therapeutic targets for personalized care of MMA pediatric patients. more...
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- 2023
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44. Evaluation of Adult and Pediatric Chiari Type 1 Malformation Patients: Do Consensus Documents Fit Everyday Practice?
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Valentini LG, Galbiati TF, Saletti V, Farinotti M, Erbetta A, Croci C, and Vetrano IG
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- Adult, Humans, Child, Consensus, Arnold-Chiari Malformation surgery, Hydrocephalus, Syringomyelia surgery
- Abstract
The management of Chiari 1 malformation (CM1) and Syringomyelia (Syr) has shown many changes in surgical indications and techniques over time. The dedicated neurosurgical and neurological community recently planned to analyze the state of the art and find conduct uniformity. This led to international consensus documents on diagnostic criteria and therapeutic strategies. We aimed to evaluate, in a large, monocentric surgical series of adult and children CM1 patients, if the daily clinical practice reflects the consensus documents. Our series comprises 190 pediatric and 220 adult Chiari patients submitted to surgery from 2000 to 2021. The main indications for the treatment were the presence of Syr and symptoms related to CM1. While there is great correspondence with the statements derived from the consensus documents about what to do for Syr and symptomatic CM1, the accordance is less evident in CM1 associated with craniosynostosis or hydrocephalus, especially when considering the early part of the series. However, we think that performing such studies could increase the homogeneity of surgical series, find a common way to evaluate long-term outcomes, and reinforce the comparability of different strategies adopted in different referral centers., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.) more...
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- 2023
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45. Chiari Malformation Type 1 and Syringomyelia: Why Do Patients Claim for International Guidelines? Commentary on the 2021 Chiari and Syringomyelia Consensus Document.
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Massimi L, Vetrano IG, Peretta P, Chiapparini L, Saletti V, Ciaramitaro P, Visocchi M, and Valentini LG
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- Adult, Humans, Child, Syringomyelia surgery, Arnold-Chiari Malformation surgery
- Abstract
The diagnosis of Chiari malformation type 1 (CM1) and Syringomyelia (Syr) has become increasingly common during the past few years. Contemporarily, the body of literature on these topics is growing, although randomized controlled studies on significant case series to drive guidelines are missing in the pediatric and adult populations. As a result of the different opinions about surgical indications and techniques raised by CM1-Syr, an increasing number of well-informed but disoriented patients is emerging. To bridge this gap, an International Consensus Conference on CM1-Syr held in Milan in November 2019 aimed to find a consensus among international experts, to suggest some recommendations that, in the near future, could lead to guidelines. Here, we comment on the most relevant recommendations about the definition, diagnosis, surgical management, failures and re-intervention, and outcome. We also focus on some "wrong" indications or techniques that, although widely disapproved by the experts, and negatively experienced by many patients, are still largely in use., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.) more...
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- 2023
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46. A Translational Approach to Spinal Neurofibromatosis: Clinical and Molecular Insights from a Wide Italian Cohort.
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Paterra R, Bettinaglio P, Borghi A, Mangano E, Tritto V, Cesaretti C, Schettino C, Bordoni R, Santoro C, Avignone S, Moscatelli M, Melone MAB, Saletti V, Piluso G, Natacci F, Riva P, and Eoli M
- Abstract
Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF’s clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33−10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1. more...
- Published
- 2022
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47. DNA methylation episignature in Gabriele-de Vries syndrome.
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Cherik F, Reilly J, Kerkhof J, Levy M, McConkey H, Barat-Houari M, Butler KM, Coubes C, Lee JA, Le Guyader G, Louie RJ, Patterson WG, Tedder ML, Bak M, Hammer TB, Craigen W, Démurger F, Dubourg C, Fradin M, Franciskovich R, Frengen E, Friedman J, Palares NR, Iascone M, Misceo D, Monin P, Odent S, Philippe C, Rouxel F, Saletti V, Strømme P, Thulin PC, Sadikovic B, and Genevieve D more...
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- DNA Methylation genetics, Genome, Humans, Male, Phenotype, Syndrome, Intellectual Disability genetics, Intellectual Disability pathology, Neurodevelopmental Disorders genetics
- Abstract
Purpose: Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and performed genome-wide DNA methylation analysis of a series of individuals carrying a YY1 variant., Methods: Clinical data were collected for 13 individuals not yet reported through an international call for collaboration. DNA was collected for 11 of these individuals and 2 previously reported individuals in an attempt to delineate a specific DNA methylation signature in GADEVS., Results: Phenotype in most individuals overlapped with the previously described features. We described 1 individual with atypical phenotype, heterozygous for a missense variant in a domain usually not involved in individuals with YY1 pathogenic missense variations. We also described a specific peripheral blood DNA methylation profile associated with YY1 variants., Conclusion: We reported a distinct DNA methylation episignature in GADEVS. We expanded the clinical profile of GADEVS to include thin/sparse hair and cryptorchidism. We also highlighted the utility of DNA methylation episignature analysis for classification of variants of unknown clinical significance., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2022
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48. Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.
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Ciaramitaro P, Massimi L, Bertuccio A, Solari A, Farinotti M, Peretta P, Saletti V, Chiapparini L, Barbanera A, Garbossa D, Bolognese P, Brodbelt A, Celada C, Cocito D, Curone M, Devigili G, Erbetta A, Ferraris M, Furlanetto M, Gilanton M, Jallo G, Karadjova M, Klekamp J, Massaro F, Morar S, Parker F, Perrini P, Poca MA, Sahuquillo J, Stoodley M, Talamonti G, Triulzi F, Valentini MC, Visocchi M, and Valentini L more...
- Subjects
- Adult, Child, Humans, Rare Diseases, Surveys and Questionnaires, Arnold-Chiari Malformation diagnosis, Arnold-Chiari Malformation diagnostic imaging, Syringomyelia diagnosis, Syringomyelia diagnostic imaging
- Abstract
Background: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing., Aim of the Study: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults., Methods: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019)., Results: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved., Conclusions: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia., (© 2021. Fondazione Società Italiana di Neurologia.) more...
- Published
- 2022
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49. Correction to: Diagnosis and treatment of Chiari Malformation and syringomyelia in adults: International Consensus Document.
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Ciaramitaro P, Massimi L, Bertuccio A, Solari A, Farinotti M, Peretta P, Saletti V, Chiapparini L, Barbanera A, Garbossa D, Bolognese P, Brodbelt A, Celada C, Cocito D, Curone M, Devigili G, Erbetta A, Ferraris M, Furlanetto M, Gilanton M, Jallo G, Karadjova M, Klekamp J, Massaro F, Morar S, Parker F, Perrini P, Poca MA, Sahuquillo J, Stoodley M, Talamonti G, Triulzi F, Valentini MC, Visocchi M, and Valentini L more...
- Published
- 2022
- Full Text
- View/download PDF
50. Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document.
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Massimi L, Peretta P, Erbetta A, Solari A, Farinotti M, Ciaramitaro P, Saletti V, Caldarelli M, Canheu AC, Celada C, Chiapparini L, Chieffo D, Cinalli G, Di Rocco F, Furlanetto M, Giordano F, Jallo G, James S, Lanteri P, Lemarchand C, Messing-Jünger M, Parazzini C, Paternoster G, Piatelli G, Poca MA, Prabahkar P, Ricci F, Righini A, Sala F, Sahuquillo J, Stoodley M, Talamonti G, Thompson D, Triulzi F, Zucchelli M, and Valentini L more...
- Subjects
- Child, Consensus, Delphi Technique, Humans, Italy, Arnold-Chiari Malformation diagnosis, Arnold-Chiari Malformation therapy, Syringomyelia
- Abstract
Background: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children., Methods: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three)., Results: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery.", Conclusions: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population., (© 2021. The Author(s).) more...
- Published
- 2022
- Full Text
- View/download PDF
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