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39 results on '"Cusin , V."'

1. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author

Denomme-Pichon A. -S., Bruel A. -L., Duffourd Y., Safraou H., Thauvin-Robinet C., Tran Mau-Them F., Philippe C., Vitobello A., Jean-Marcais N., Moutton S., Thevenon J., Faivre L., Matalonga L., de Boer E., Gilissen C., Hoischen A., Kleefstra T., Pfundt R., de Vries B. B. A., Willemsen M. H., Vissers L. E. L. M., Jackson A., Banka S., Clayton-Smith J., Benetti E., Fallerini C., Renieri A., Ciolfi A., Dallapiccola B., Pizzi S., Radio F. C., Tartaglia M., Ellwanger K., Graessner H., Haack T. B., Zurek B., Havlovicova M., Macek M., Ryba L., Schwarz M., Votypka P., Lopez-Martin E., Posada M., Mencarelli M. A., Rooryck C., Trimouille A., Verloes A., Abbott K. M., Kerstjens M., Martin E. L., Maystadt I., Morleo M., Nigro V., Pinelli M., Riess O., Agathe J. -M. D. S., Santen G. W. E., Thauvin C., Torella A., Vissers L., Zguro K., Boer E. D., Cohen E., Danis D., Gao F., Horvath R., Johari M., Johanson L., Li S., Morsy H., Nelson I., Paramonov I., te Paske I. B. A. W., Robinson P., Savarese M., Steyaert W., Topf A., van der Velde J. K., Vandrovcova J., Ossowski S., Demidov G., Sturm M., Schulze-Hentrich J. M., Schule R., Xu J., Kessler C., Wayand M., Synofzik M., Wilke C., Traschutz A., Schols L., Hengel H., Lerche H., Kegele J., Heutink P., Brunner H., Scheffer H., Hoogerbrugge N., 't Hoen P. A. C., Sablauskas K., de Voer R. M., Kamsteeg E. -J., van de Warrenburg B., van Os N., Paske I. T., Janssen E., Steehouwer M., Yaldiz B., Brookes A. J., Veal C., Gibson S., Maddi V., Mehtarizadeh M., Riaz U., Warren G., Dizjikan F. Y., Shorter T., Straub V., Bettolo C. M., Manera J. D., Hambleton S., Engelhardt K., Alexander E., Peyron C., Pelissier A., Beltran S., Gut I. G., Laurie S., Piscia D., Papakonstantinou A., Bullich G., Corvo A., Fernandez-Callejo M., Hernandez C., Pico D., Lochmuller H., Gumus G., Bros-Facer V., Rath A., Hanauer M., Lagorce D., Hongnat O., Chahdil M., Lebreton E., Stevanin G., Durr A., Davoine C. -S., Guillot-Noel L., Heinzmann A., Coarelli G., Bonne G., Evangelista T., Allamand V., Ben Yaou R., Metay C., Eymard B., Atalaia A., Stojkovic T., Turnovec M., Thomasova D., Kremlikova R. P., Frankova V., Liskova P., Dolezalova P., Parkinson H., Keane T., Freeberg M., Thomas C., Spalding D., Robert G., Costa A., Patch C., Hanna M., Houlden H., Reilly M., Efthymiou S., Cali E., Magrinelli F., Sisodiya S. M., Rohrer J., Muntoni F., Zaharieva I., Sarkozy A., Timmerman V., Baets J., de Vries G., De Winter J., Beijer D., de Jonghe P., Van de Vondel L., De Ridder W., Weckhuysen S., Mutarelli M., Varavallo A., Banfi S., Musacchia F., Piluso G., Ferlini A., Selvatici R., Gualandi F., Bigoni S., Rossi R., Neri M., Aretz S., Spier I., Sommer A. K., Peters S., Oliveira C., Pelaez J. G., Matos A. R., Jose C. S., Ferreira M., Gullo I., Fernandes S., Garrido L., Ferreira P., Carneiro F., Swertz M. A., Johansson L., van der Vries G., Neerincx P. B., Ruvolo D., Kerstjens Frederikse W. S., Zonneveld-Huijssoon E., Roelofs-Prins D., van Gijn M., Kohler S., Metcalfe A., Drunat S., Heron D., Mignot C., Keren B., Lacombe D., Capella G., Valle L., Holinski-Feder E., Laner A., Steinke-Lange V., Cilio M. -R., Carpancea E., Depondt C., Lederer D., Sznajer Y., Duerinckx S., Mary S., Macaya A., Cazurro-Gutierrez A., Perez-Duenas B., Munell F., Jarava C. F., Maso L. B., Marce-Grau A., Colobran R., Hackman P., Udd B., Hemelsoet D., Dermaut B., Schuermans N., Poppe B., Verdin H., Osorio A. N., Depienne C., Roos A., Cordts I., Deschauer M., Striano P., Zara F., Riva A., Iacomino M., Uva P., Scala M., Scudieri P., Basak A. N., Claeys K., Boztug K., Haimel M., W. E G., Ruivenkamp C. A. L., Natera de Benito D., Thompson R., Polavarapu K., Grimbacher B., Zaganas I., Kokosali E., Lambros M., Evangeliou A., Spilioti M., Kapaki E., Bourbouli M., Balicza P., Molnar M. J., De la Paz M. P., Sanchez E. B., Delgado B. M., Alonso Garcia de la Rosa F. J., Schrock E., Rump A., Mei D., Vetro A., Balestrini S., Guerrini R., Chinnery P. F., Ratnaike T., Schon K., Maver A., Peterlin B., Munchau A., Lohmann K., Herzog R., Pauly M., May P., Beeson D., Cossins J., Furini S., Afenjar A., Goldenberg A., Masurel A., Phan A., Dieux-Coeslier A., Fargeot A., Guerrot A. -M., Toutain A., Molin A., Sorlin A., Putoux A., Jouret B., Laudier B., Demeer B., Doray B., Bonniaud B., Isidor B., Gilbert-Dussardier B., Leheup B., Reversade B., Paul C., Vincent-Delorme C., Neiva C., Poirsier C., Quelin C., Chiaverini C., Coubes C., Francannet C., Colson C., Desplantes C., Wells C., Goizet C., Sanlaville D., Amram D., Lehalle D., Genevieve D., Gaillard D., Zivi E., Sarrazin E., Steichen E., Schaefer E., Lacaze E., Jacquemin E., Bongers E., Kilic E., Colin E., Giuliano F., Prieur F., Laffargue F., Morice-Picard F., Petit F., Cartault F., Feillet F., Baujat G., Morin G., Diene G., Journel H., Perthus I., Lespinasse J., Alessandri J. -L., Amiel J., Martinovic J., Delanne J., Albuisson J., Lambert L., Perrin L., Ousager L. B., Van Maldergem L., Pinson L., Ruaud L., Samimi M., Bournez M., Bonnet-Dupeyron M. N., Vincent M., Jacquemont M. -L., Cordier-Alex M. -P., Gerard-Blanluet M., Willems M., Spodenkiewicz M., Doco-Fenzy M., Rossi M., Renaud M., Fradin M., Mathieu M., Holder-Espinasse M. H., Houcinat N., Hanna N., Leperrier N., Chassaing N., Philip N., Boute O., Van Kien P. K., Parent P., Bitoun P., Sarda P., Vabres P., Jouk P. -S., Touraine R., El Chehadeh S., Whalen S., Marlin S., Passemard S., Grotto S., Bellanger S. A., Blesson S., Nambot S., Naudion S., Lyonnet S., Odent S., Attie-Bitach T., Busa T., Drouin-Garraud V., Layet V., Bizaoui V., Cusin V., Capri Y., Alembik Y., Unión Europea. Comisión Europea. H2020, Unión Europea. Comisión Europea. 7 Programa Marco, Instituto de Salud Carlos III, Instituto Nacional de Bioinformatica (España), Ministry of Health (República Checa), Ministry of Education, Youth and Sports (República Checa), Denomme-Pichon, A. -S., Bruel, A. -L., Duffourd, Y., Safraou, H., Thauvin-Robinet, C., Tran Mau-Them, F., Philippe, C., Vitobello, A., Jean-Marcais, N., Moutton, S., Thevenon, J., Faivre, L., Matalonga, L., de Boer, E., Gilissen, C., Hoischen, A., Kleefstra, T., Pfundt, R., de Vries, B. B. A., Willemsen, M. H., Vissers, L. E. L. M., Jackson, A., Banka, S., Clayton-Smith, J., Benetti, E., Fallerini, C., Renieri, A., Ciolfi, A., Dallapiccola, B., Pizzi, S., Radio, F. C., Tartaglia, M., Ellwanger, K., Graessner, H., Haack, T. B., Zurek, B., Havlovicova, M., Macek, M., Ryba, L., Schwarz, M., Votypka, P., Lopez-Martin, E., Posada, M., Mencarelli, M. A., Rooryck, C., Trimouille, A., Verloes, A., Abbott, K. M., Kerstjens, M., Martin, E. L., Maystadt, I., Morleo, M., Nigro, V., Pinelli, M., Riess, O., Agathe, J. -M. D. S., Santen, G. W. E., Thauvin, C., Torella, A., Vissers, L., Zguro, K., Boer, E. D., Cohen, E., Danis, D., Gao, F., Horvath, R., Johari, M., Johanson, L., Li, S., Morsy, H., Nelson, I., Paramonov, I., te Paske, I. B. A. W., Robinson, P., Savarese, M., Steyaert, W., Topf, A., van der Velde, J. K., Vandrovcova, J., Ossowski, S., Demidov, G., Sturm, M., Schulze-Hentrich, J. M., Schule, R., Xu, J., Kessler, C., Wayand, M., Synofzik, M., Wilke, C., Traschutz, A., Schols, L., Hengel, H., Lerche, H., Kegele, J., Heutink, P., Brunner, H., Scheffer, H., Hoogerbrugge, N., 't Hoen, P. A. C., Sablauskas, K., de Voer, R. M., Kamsteeg, E. -J., van de Warrenburg, B., van Os, N., Paske, I. T., Janssen, E., Steehouwer, M., Yaldiz, B., Brookes, A. J., Veal, C., Gibson, S., Maddi, V., Mehtarizadeh, M., Riaz, U., Warren, G., Dizjikan, F. Y., Shorter, T., Straub, V., Bettolo, C. M., Manera, J. D., Hambleton, S., Engelhardt, K., Alexander, E., Peyron, C., Pelissier, A., Beltran, S., Gut, I. G., Laurie, S., Piscia, D., Papakonstantinou, A., Bullich, G., Corvo, A., Fernandez-Callejo, M., Hernandez, C., Pico, D., Lochmuller, H., Gumus, G., Bros-Facer, V., Rath, A., Hanauer, M., Lagorce, D., Hongnat, O., Chahdil, M., Lebreton, E., Stevanin, G., Durr, A., Davoine, C. -S., Guillot-Noel, L., Heinzmann, A., Coarelli, G., Bonne, G., Evangelista, T., Allamand, V., Ben Yaou, R., Metay, C., Eymard, B., Atalaia, A., Stojkovic, T., Turnovec, M., Thomasova, D., Kremlikova, R. P., Frankova, V., Liskova, P., Dolezalova, P., Parkinson, H., Keane, T., Freeberg, M., Thomas, C., Spalding, D., Robert, G., Costa, A., Patch, C., Hanna, M., Houlden, H., Reilly, M., Efthymiou, S., Cali, E., Magrinelli, F., Sisodiya, S. M., Rohrer, J., Muntoni, F., Zaharieva, I., Sarkozy, A., Timmerman, V., Baets, J., de Vries, G., De Winter, J., Beijer, D., de Jonghe, P., Van de Vondel, L., De Ridder, W., Weckhuysen, S., Mutarelli, M., Varavallo, A., Banfi, S., Musacchia, F., Piluso, G., Ferlini, A., Selvatici, R., Gualandi, F., Bigoni, S., Rossi, R., Neri, M., Aretz, S., Spier, I., Sommer, A. K., Peters, S., Oliveira, C., Pelaez, J. G., Matos, A. R., Jose, C. S., Ferreira, M., Gullo, I., Fernandes, S., Garrido, L., Ferreira, P., Carneiro, F., Swertz, M. A., Johansson, L., van der Vries, G., Neerincx, P. B., Ruvolo, D., Kerstjens Frederikse, W. S., Zonneveld-Huijssoon, E., Roelofs-Prins, D., van Gijn, M., Kohler, S., Metcalfe, A., Drunat, S., Heron, D., Mignot, C., Keren, B., Lacombe, D., Capella, G., Valle, L., Holinski-Feder, E., Laner, A., Steinke-Lange, V., Cilio, M. -R., Carpancea, E., Depondt, C., Lederer, D., Sznajer, Y., Duerinckx, S., Mary, S., Macaya, A., Cazurro-Gutierrez, A., Perez-Duenas, B., Munell, F., Jarava, C. F., Maso, L. B., Marce-Grau, A., Colobran, R., Hackman, P., Udd, B., Hemelsoet, D., Dermaut, B., Schuermans, N., Poppe, B., Verdin, H., Osorio, A. N., Depienne, C., Roos, A., Cordts, I., Deschauer, M., Striano, P., Zara, F., Riva, A., Iacomino, M., Uva, P., Scala, M., Scudieri, P., Basak, A. N., Claeys, K., Boztug, K., Haimel, M., W. E, G., Ruivenkamp, C. A. L., Natera de Benito, D., Thompson, R., Polavarapu, K., Grimbacher, B., Zaganas, I., Kokosali, E., Lambros, M., Evangeliou, A., Spilioti, M., Kapaki, E., Bourbouli, M., Balicza, P., Molnar, M. J., De la Paz, M. P., Sanchez, E. B., Delgado, B. M., Alonso Garcia de la Rosa, F. J., Schrock, E., Rump, A., Mei, D., Vetro, A., Balestrini, S., Guerrini, R., Chinnery, P. F., Ratnaike, T., Schon, K., Maver, A., Peterlin, B., Munchau, A., Lohmann, K., Herzog, R., Pauly, M., May, P., Beeson, D., Cossins, J., Furini, S., Afenjar, A., Goldenberg, A., Masurel, A., Phan, A., Dieux-Coeslier, A., Fargeot, A., Guerrot, A. -M., Toutain, A., Molin, A., Sorlin, A., Putoux, A., Jouret, B., Laudier, B., Demeer, B., Doray, B., Bonniaud, B., Isidor, B., Gilbert-Dussardier, B., Leheup, B., Reversade, B., Paul, C., Vincent-Delorme, C., Neiva, C., Poirsier, C., Quelin, C., Chiaverini, C., Coubes, C., Francannet, C., Colson, C., Desplantes, C., Wells, C., Goizet, C., Sanlaville, D., Amram, D., Lehalle, D., Genevieve, D., Gaillard, D., Zivi, E., Sarrazin, E., Steichen, E., Schaefer, E., Lacaze, E., Jacquemin, E., Bongers, E., Kilic, E., Colin, E., Giuliano, F., Prieur, F., Laffargue, F., Morice-Picard, F., Petit, F., Cartault, F., Feillet, F., Baujat, G., Morin, G., Diene, G., Journel, H., Perthus, I., Lespinasse, J., Alessandri, J. -L., Amiel, J., Martinovic, J., Delanne, J., Albuisson, J., Lambert, L., Perrin, L., Ousager, L. B., Van Maldergem, L., Pinson, L., Ruaud, L., Samimi, M., Bournez, M., Bonnet-Dupeyron, M. N., Vincent, M., Jacquemont, M. -L., Cordier-Alex, M. -P., Gerard-Blanluet, M., Willems, M., Spodenkiewicz, M., Doco-Fenzy, M., Rossi, M., Renaud, M., Fradin, M., Mathieu, M., Holder-Espinasse, M. H., Houcinat, N., Hanna, N., Leperrier, N., Chassaing, N., Philip, N., Boute, O., Van Kien, P. K., Parent, P., Bitoun, P., Sarda, P., Vabres, P., Jouk, P. -S., Touraine, R., El Chehadeh, S., Whalen, S., Marlin, S., Passemard, S., Grotto, S., Bellanger, S. A., Blesson, S., Nambot, S., Naudion, S., Lyonnet, S., Odent, S., Attie-Bitach, T., Busa, T., Drouin-Garraud, V., Layet, V., Bizaoui, V., Cusin, V., Capri, Y., Alembik, Y., and Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center]

Subjects
Exome reanalysis, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Multidisciplinaire, généralités & autres [D99] [Sciences de la santé humaine], Developmental disorder, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Biology and Life Sciences, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], ClinVar, Rare diseases, All institutes and research themes of the Radboud University Medical Center, Medicine and Health Sciences, Genetics & genetic processes [F10] [Life sciences], Génétique & processus génétiques [F10] [Sciences du vivant], Multidisciplinary, general & others [D99] [Human health sciences], Exome reanalysi, Genetics (clinical)
Abstract

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion: The "ClinVar low-hanging fruit" analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M. Sí

Published
2023

2. Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

Author

Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Y, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Van Kien, Khau P, Baumann, C, Leheup, B, Coignard, Martin- D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Boidron, Mosca- AL, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, and Faivre, L

Published
2013
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5. INCIDENCE OF COLORECTAL NEOPLASIA AMONG YOUNG PATIENTS WITH LYNCH SYNDROME IN CORRELATION WITH THE TYPE OF MUTATION: RESULTS OF THE LARGEST PARIS AREA COHORT

Author

Coffin, E, additional, Lekhal, C, additional, Perrod, G, additional, Samaha, E, additional, Cuadrado, E Perez, additional, Colas, C, additional, Dhooge, M, additional, Netter-Cotti, J, additional, Caron, O, additional, Cusin, V, additional, Perkins, G, additional, Zaanan, A, additional, Buecher, B, additional, Bellanger, J, additional, Parc, Y, additional, Malka, D, additional, Chaussade, S, additional, Puig, P Laurent, additional, Benamouzig, R, additional, and Cellier, C, additional

Published
2020
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10. Genetic heterogeneity in Leri-Weill dyschondrosteosis

Author

Huber, C., Cusin, V., Dagoneau, N., Le Merrer, M., Munnich, A., and Cormier-Daire, V.

Subjects
Genetic research -- Analysis, Human genetics -- Research, Genetic disorders -- Research, Biological sciences
Published
2000

11. Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Yves, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Khau Van Kien, P, Baumann, C, Leheup, B, Martin-Coignard, D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Mosca-Boidron, A L, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, Faivre, L, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Yves, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Khau Van Kien, P, Baumann, C, Leheup, B, Martin-Coignard, D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Mosca-Boidron, A L, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, and Faivre, L

Abstract

The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.

Published
2013

15. The power of high-resolution non-targeted array-CGH in identifying intragenic rearrangements responsible for Cohen syndrome

Author

El Chehadeh-Djebbar, S., primary, Faivre, L., additional, Moncla, A., additional, Aral, B., additional, Missirian, C., additional, Popovici, C., additional, Rump, P., additional, Van Essen, A., additional, Frances, A.-M., additional, Gigot, N., additional, Cusin, V., additional, Masurel-Paulet, A., additional, Gueneau, L., additional, Payet, M., additional, Ragon, C., additional, Marle, N., additional, Mosca-Boidron, A.-L., additional, Huet, F., additional, Balikova, I., additional, Teyssier, J.-R., additional, Mugneret, F., additional, Thauvin-Robinet, C., additional, and Callier, P., additional

Published
2011
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16. Cloacal exstrophy in an infant with 9q34.1-qter deletion resulting from a de novo unbalanced translocation between chromosome 9q and Yq

Author

Thauvin-Robinet, Christel, primary, Faivre, Laurence, additional, Cusin, V�ronica, additional, Khau Van Kien, Philippe, additional, Callier, Patrick, additional, Parker, Keith L., additional, Fellous, Marc, additional, Borgnon, Jos�phine, additional, Gounot, Emmanuel, additional, Huet, Fr�d�ric, additional, Sapin, Emmanuel, additional, and Mugneret, Francine, additional

Published
2004
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19. Exclusion of chromosome 9 helps to identify mild variants of acromesomelic dysplasia Maroteaux type

Author

Faivre, L., Merrer, M. Le, Cusin, V., Munnich, A., Maroteaux, P., Cormier-Daire, V., Megarbane, A., Gilbert, B., and Mortier, G.

Abstract

Acromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive disorder belonging to the group of acromesomelic dysplasias. AMDM is characterised by severe dwarfism with shortening of the middle and distal segments of the limbs. An AMDM gene has recently been mapped to human chromosome 9p13-q12 by homozygosity mapping in four consanguineous families. Here, we show linkage of the disease gene to chromosome 9p13-q12 in four of five consanguineous AMDM families and its exclusion in a fifth family with two children affected with a mild form of the disease. This study suggests that genetic heterogeneity accounts for the variable clinical and radiological severity of AMDM.

Published
2000

20. Les gestes du formateur d’enseignants

Author

Gagnon, Roxane, Dolz, Joaquim, Equipe FORENDIF (dont Marmy Cusin, V.), Gagnon, Roxane, Dolz, Joaquim, and Equipe FORENDIF (dont Marmy Cusin, V.)

21. Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Author

Gerasimenko A, Mignot C, Naggara O, Coulet F, Ekram S, Heide S, Sorato C, Mazowiecki M, Perrin L, Colas C, Cusin V, Caux F, Dardenne A, El Chehadeh S, Verloes A, Maurey H, Afenjar A, Petit F, Barete S, Boespflug-Tanguy O, Bourrat E, Capri Y, Ciorna V, Deb W, Doummar D, Perrier A, Guédon A, Houdart E, Isidor B, Jacquemont ML, Buffet C, Mercier S, Passemard S, Riquet A, Ruaud L, Schaefer E, Heron D, Bisdorff A, and Benusiglio PR

Subjects
Humans, Adult, Female, Male, Young Adult, Magnetic Resonance Imaging, Mutation, PTEN Phosphohydrolase genetics, Central Nervous System Vascular Malformations genetics, Central Nervous System Vascular Malformations complications, Central Nervous System Vascular Malformations diagnostic imaging, Central Nervous System Vascular Malformations diagnosis, Hamartoma Syndrome, Multiple genetics, Hamartoma Syndrome, Multiple complications
Abstract

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Published
2024
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22. Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry.

Author

Alric H, Coffin E, Lekhal C, Benusiglio PR, Dhooge M, Colas C, Caron O, Cusin V, Becq A, Perez Cuadrado Robles E, Leenhardt R, Perkins G, Buecher B, Bellanger J, Rahmi G, Malka D, Laurent-Puig P, Chaussade S, Benamouzig R, Parc Y, Cellier C, and Perrod G

Subjects
Humans, Male, Adult, Middle Aged, Female, Colonoscopy, Germ-Line Mutation, DNA Mismatch Repair, Colorectal Neoplasms, Hereditary Nonpolyposis epidemiology, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Colorectal Neoplasms diagnosis, Adenoma epidemiology, Adenoma genetics, Adenoma diagnosis
Abstract

Background: Lynch syndrome (LS) is the most frequent inherited colorectal cancer syndrome., Aim: To assess the burden of adenoma in LS patients under 50 years-old followed in the PRED-IdF network., Methods: From January 2010 to January 2019, all patients under 50 years of age with a confirmed LS germline mutation were included. The main objective was the description of adenomas characteristics according to path&#95;MMR., Results: We analyzed data from 708 patients (mean age 34.8 ± 8.6), of which 41.8 % were male. Among these patients, 37.6% had path&#95;MLH1, 45.4% path&#95;MSH2, 13.9% path&#95;MSH6, 2.9% path&#95;PMS2, and 1.2% path&#95;EpCAM. The analysis included 1721 (70.9%) follow-up colonoscopies. A total of 682 adenomas were detected, including 140 (20.5%) advanced adenomas. The adenoma detection rates during the first and follow-up colonoscopies were 19.2% and 20.5%, respectively. Most adenomas were <10 mm (57.9%), located in the proximal colon (334, 48.9%), and presented as non-polypoid lesions (493, 72.3%). The median growth time for adenomas was 23 months (range 9-114) irrespective of the path&#95;MMR mutation (p = 0.62)., Conclusion: LS patients under 50 years of age have a high burden of adenomas, particularly small non-polypoid adenomas located in the proximal colon. These results highlight the need for intensive screening, with a particular focus on the proximal colon., Competing Interests: Declaration of Competing Interest Authors declare no Conflict of Interests for this article., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2024
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23. Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.

Author

Caputo SM, Golmard L, Léone M, Damiola F, Guillaud-Bataille M, Revillion F, Rouleau E, Derive N, Buisson A, Basset N, Schwartz M, Vilquin P, Garrec C, Privat M, Gay-Bellile M, Abadie C, Abidallah K, Airaud F, Allary AS, Barouk-Simonet E, Belotti M, Benigni C, Benusiglio PR, Berthemin C, Berthet P, Bertrand O, Bézieau S, Bidart M, Bignon YJ, Birot AM, Blanluet M, Bloucard A, Bombled J, Bonadona V, Bonnet F, Bonnet-Dupeyron MN, Boulaire M, Boulouard F, Bouras A, Bourdon V, Brahimi A, Brayotel F, Bressac de Paillerets B, Bronnec N, Bubien V, Buecher B, Cabaret O, Carriere J, Chiesa J, Chieze-Valéro S, Cohen C, Cohen-Haguenauer O, Colas C, Collonge-Rame MA, Conoy AL, Coulet F, Coupier I, Crivelli L, Cusin V, De Pauw A, Dehainault C, Delhomelle H, Delnatte C, Demontety S, Denizeau P, Devulder P, Dreyfus H, d'Enghein CD, Dupré A, Durlach A, Dussart S, Fajac A, Fekairi S, Fert-Ferrer S, Fiévet A, Fouillet R, Mouret-Fourme E, Gauthier-Villars M, Gesta P, Giraud S, Gladieff L, Goldbarg V, Goussot V, Guibert V, Guillerm E, Guy C, Hardouin A, Heude C, Houdayer C, Ingster O, Jacquot-Sawka C, Jones N, Krieger S, Lacoste S, Lallaoui H, Larbre H, Laugé A, Le Guyadec G, Le Mentec M, Lecerf C, Le Gall J, Legendre B, Legrand C, Legros A, Lejeune S, Lidereau R, Lignon N, Limacher JM, Doriane Livon, Lizard S, Longy M, Lortholary A, Macquere P, Mailliez A, Malsa S, Margot H, Mari V, Maugard C, Meira C, Menjard J, Molière D, Moncoutier V, Moretta-Serra J, Muller E, Nevière Z, Nguyen Minh Tuan TV, Noguchi T, Noguès C, Oca F, Popovici C, Prieur F, Raad S, Rey JM, Ricou A, Salle L, Saule C, Sevenet N, Simaga F, Sobol H, Suybeng V, Tennevet I, Tenreiro H, Tinat J, Toulas C, Turbiez I, Uhrhammer N, Vande Perre P, Vaur D, Venat L, Viellard N, Villy MC, Warcoin M, Yvard A, Zattara H, Caron O, Lasset C, Remenieras A, Boutry-Kryza N, Castéra L, and Stoppa-Lyonnet D

Subjects
Breast Neoplasms classification, Breast Neoplasms genetics, Female, Genetic Testing, Genotype, Humans, Ovarian Neoplasms classification, Ovarian Neoplasms genetics, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms pathology, Genetic Predisposition to Disease, Genetic Variation, Ovarian Neoplasms pathology
Abstract

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs. The classification method was a multifactorial model combining different associations between VUSs and cancer, including cosegregation data. At this time, among the 653 variants selected, 101 (15%) distinct variants shared by 1,624 families were classified as pathogenic/likely pathogenic or benign/likely benign by the COVAR study. Sixty-six of the 101 (65%) variants classified by COVAR would have remained VUSs without cosegregation data. Of note, among the 34 variants classified as pathogenic by COVAR, 16 remained VUSs or likely pathogenic when following the ACMG/AMP variant classification guidelines. Although the initiation and organization of cosegregation analyses require a considerable effort, the growing number of available genetic tests results in an increasing number of families sharing a particular variant, and thereby increases the power of such analyses. Here we demonstrate that variant cosegregation analyses are a powerful tool for the classification of variants in the BRCA1/2 breast-ovarian cancer predisposition genes., Competing Interests: Declaration of interests D.S.-L. and the Institut Curie have received honoraria for her participation in education meetings organized by AstraZeneca or Tesaro. The remaining authors declare no conflict of interest., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2021
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24. Further delineation of the NTHL1 associated syndrome: A report from the French Oncogenetic Consortium.

Author

Boulouard F, Kasper E, Buisine MP, Lienard G, Vasseur S, Manase S, Bahuau M, Barouk Simonet E, Bubien V, Coulet F, Cusin V, Dhooge M, Golmard L, Goussot V, Hamzaoui N, Lacaze E, Lejeune S, Mauillon J, Beaumont MP, Pinson S, Tlemsani C, Toulas C, Rey JM, Uhrhammer N, Bougeard G, Frebourg T, Houdayer C, and Baert-Desurmont S

Subjects
Adenomatous Polyposis Coli genetics, Adult, Aged, Biomarkers, Tumor genetics, Breast Neoplasms genetics, Colorectal Neoplasms genetics, Female, Germ-Line Mutation, Heterozygote, Humans, Male, Middle Aged, Pedigree, Reverse Transcriptase Polymerase Chain Reaction, Deoxyribonuclease (Pyrimidine Dimer) genetics, Neoplastic Syndromes, Hereditary genetics, Ovarian Neoplasms genetics
Abstract

Biallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra-colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the "colorectal cancer or polyposis" series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra-digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra-colonic surveillance has to be defined., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2021
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25. Clinical implications of CTNNA1 germline mutations in asymptomatic carriers.

Author

Benusiglio PR, Colas C, Guillerm E, Canard A, Delhomelle H, Warcoin M, Bellanger J, Eyries M, Zizi M, Netter J, Soubrier F, Parc Y, Mourregot A, Maran Gonzalez A, Cusin V, Denis JA, Coupier I, Svrcek M, and Coulet F

Subjects
Adult, Carcinoma, Signet Ring Cell metabolism, Carcinoma, Signet Ring Cell pathology, Carcinoma, Signet Ring Cell surgery, Female, Follow-Up Studies, Gastrectomy, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Pedigree, Prognosis, Retrospective Studies, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Stomach Neoplasms surgery, alpha Catenin metabolism, Asymptomatic Diseases therapy, Carcinoma, Signet Ring Cell genetics, Germ-Line Mutation, Stomach Neoplasms genetics, alpha Catenin genetics
Abstract

In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.

Published
2019
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26. [The French Genetic and Cancer Consortium guidelines for multigene panel analysis in hereditary breast and ovarian cancer predisposition].

Author

Moretta J, Berthet P, Bonadona V, Caron O, Cohen-Haguenauer O, Colas C, Corsini C, Cusin V, De Pauw A, Delnatte C, Dussart S, Jamain C, Longy M, Luporsi E, Maugard C, Nguyen TD, Pujol P, Vaur D, Andrieu N, Lasset C, and Noguès C

Subjects
Antigens, CD, Cadherins, DNA-Binding Proteins genetics, Epithelial Cell Adhesion Molecule genetics, Fanconi Anemia Complementation Group N Protein genetics, Female, France, Genes, BRCA1, Genes, BRCA2, Genes, p53, Genetic Markers genetics, Humans, Mismatch Repair Endonuclease PMS2 genetics, MutL Protein Homolog 1 genetics, MutS Homolog 2 Protein genetics, PTEN Phosphohydrolase genetics, Breast Neoplasms genetics, Genetic Predisposition to Disease genetics, Ovarian Neoplasms genetics
Abstract

Introduction: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed., Methods: The French Genetic and Cancer Group (GGC) - Unicancer conducted an exhaustive bibliographic work on 18 genes of interest. Only publications with unbiased risk estimates were retained., Results: The expertise of each 18 genes was based on clinical utility criteria, i.e. a relative risk of cancer of 4 and more, available medical tools for screening and prevention of mutation carriers, and pre-symptomatic genetic tests for relatives. Finally, 13 genes were selected to be included in a HBOC diagnosis gene panel: BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM. The reasons for excluding NBN, RAD51B, CHEK2, STK11, ATM, BARD1, BRIP1 from the HBOC diagnosis panel are presented. Screening, prevention and genetic counselling guidelines were detailed for each of the 18 genes., Discussion: Due to the rapid increase in knowledge, the GGC has planned a yearly update of the bibliography to take into account new findings. Furthermore, genetic-epidemiological studies are being initiated to better estimate the cancer risk associated with genes which are not yet included in the HBOC diagnosis panel., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Published
2018
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27. Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

Author

Aubart M, Gobert D, Aubart-Cohen F, Detaint D, Hanna N, d'Indya H, Lequintrec JS, Renard P, Vigneron AM, Dieudé P, Laissy JP, Koch P, Muti C, Roume J, Cusin V, Grandchamp B, Gouya L, LeGuern E, Papo T, Boileau C, and Jondeau G

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Death, Sudden, Female, Humans, Male, Middle Aged, Pedigree, Phenotype, Syndrome, Young Adult, Aortic Dissection genetics, Aortic Aneurysm, Thoracic genetics, Autoimmune Diseases genetics, Charcot-Marie-Tooth Disease genetics, Mutation, Osteoarthritis genetics, Smad3 Protein genetics
Abstract

Background: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined., Methods: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases., Results: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients., Interpretation: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

Published
2014
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28. Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma.

Author

Gardie B, Remenieras A, Kattygnarath D, Bombled J, Lefèvre S, Perrier-Trudova V, Rustin P, Barrois M, Slama A, Avril MF, Bessis D, Caron O, Caux F, Collignon P, Coupier I, Cremin C, Dollfus H, Dugast C, Escudier B, Faivre L, Field M, Gilbert-Dussardier B, Janin N, Leport Y, Leroux D, Lipsker D, Malthieu F, McGilliwray B, Maugard C, Méjean A, Mortemousque I, Plessis G, Poppe B, Pruvost-Balland C, Rooker S, Roume J, Soufir N, Steinraths M, Tan MH, Théodore C, Thomas L, Vabres P, Van Glabeke E, Meric JB, Verkarre V, Lenoir G, Joulin V, Deveaux S, Cusin V, Feunteun J, Teh BT, Bressac-de Paillerets B, and Richard S

Subjects
Adult, Aged, Cell Line, Tumor, Codon, Nonsense, Female, Frameshift Mutation, Gene Deletion, Gene Rearrangement, Genotype, Germ-Line Mutation, Humans, INDEL Mutation, Leiomyomatosis congenital, Leiomyomatosis genetics, Male, Middle Aged, Mutation, Missense, Neoplastic Syndromes, Hereditary, Pedigree, Skin Neoplasms, Uterine Neoplasms, Carcinoma, Renal Cell genetics, Fumarate Hydratase genetics, Kidney Neoplasms genetics, Mutation
Abstract

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder predisposing humans to cutaneous and uterine leiomyomas; in 20% of affected families, type 2 papillary renal cell cancers (PRCCII) also occur with aggressive course and poor prognosis. HLRCC results from heterozygous germline mutations in the tumour suppressor fumarate hydratase (FH) gene., Methods: As part of the French National Cancer Institute (INCa) 'Inherited predispositions to kidney cancer' network, sequence analysis and a functional study of FH were preformed in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic)., Results: The study identified 32 different germline FH mutations (15 missense, 6 frameshifts, 4 nonsense, 1 deletion/insertion, 5 splice site, and 1 complete deletion) in 40/56 (71.4%) families with proven or suspected HLRCC and in 4/23 (17.4%) probands with PRCCII alone, including 2 sporadic cases. 21 of these were novel and all were demonstrated as deleterious by significant reduction of FH enzymatic activity. In addition, 5 asymptomatic parents in 3 families were confirmed as carrying disease-causing mutations., Conclusions: This study identified and characterised 21 novel FH mutations and demonstrated that PRCCII can be the only one manifestation of HLRCC. Due to the incomplete penetrance of HLRCC, the authors propose to extend the FH mutation analysis to every patient with PRCCII occurring before 40 years of age or when renal tumour harbours characteristic histologic features, in order to discover previously ignored HLRCC affected families.

Published
2011
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29. A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease.

Author

Latour P, Thauvin-Robinet C, Baudelet-Méry C, Soichot P, Cusin V, Faivre L, Locatelli MC, Mayençon M, Sarcey A, Broussolle E, Camu W, David A, and Rousson R

Subjects
Adolescent, Adult, Amino Acid Sequence, Aminoacylation, Child, Cohort Studies, Genes, Dominant, Humans, Lod Score, Middle Aged, Molecular Sequence Data, Pedigree, Sequence Homology, Amino Acid, Alanine-tRNA Ligase genetics, Axons metabolism, Charcot-Marie-Tooth Disease genetics, Cytoplasm metabolism, Mutation
Abstract

Charcot-Marie-Tooth disease (CMT) is the most common cause of inherited peripheral neuropathy, with an estimated frequency of 1/2500. We studied a large family with 17 patients affected by the axonal form of CMT (CMT2). Analysis of the 15 genes or loci known to date was negative. Genome-wide genotyping identified a CMT2 locus in 16q21-q23 between D16S3050 and D16S3106. The maximum two-point LOD score was 4.77 at theta = 0 for marker D16S3050. Sequencing of candidate genes identified a unique mutation, c.986G>A (p.Arg329His), affecting a totally conserved amino acid in the helical domain of cytoplasmic alanyl-tRNA synthetase (AlaRS). A second family with the same mutation and a different founder was then identified in a cohort of 91 CMT2 families. Although mislocation of mutant Arg329His-AlaRS in axons remains to be evaluated, experimental data point mostly to a quantitative reduction in tRNA(Ala) aminoacylation. Aminoacylation and editing functions closely cooperate in AlaRS, and Arg329His mutation could also lead to qualitative errors participating in neurodegeneration. Our report documents in 18 patients the deleterious impact of a mutation in human cytoplasmic AlaRS and broadens the spectrum of defects found in tRNA synthetases. Patients present with sensory-motor distal degeneration secondary to predominant axonal neuropathy, slight demyelination, and no atypical or additional CNS features., (2010 The American Society of Human Genetics. Published by Elsevier Inc.)

Published
2010
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30. Spondylocostal dysostosis, anal and genitourinary malformations in a fetal case: a new case of Casamassima-Morton-Nance syndrome?

Author

Thauvin-Robinet C, Laurent N, Rousseau T, Couvreur S, Cusin V, Callier P, Mugneret F, Durand C, Huet F, Sagot P, and Faivre L

Subjects
Dysostoses genetics, Fetus abnormalities, Humans, Ribs abnormalities, Spine abnormalities, Syndrome, Abnormalities, Multiple genetics, Anal Canal abnormalities, Dysostoses pathology, Urogenital Abnormalities genetics
Abstract

Casamassima-Morton-Nance syndrome belongs to the heterogeneous group of spondylocostal dysostoses (SCD) represented by a large heterogeneous group in which diverse diagnoses, associations and modes of inheritance are found. Common features include segmentation abnormalities of the vertebrae and ribs. Here, we report on a fetal case with spondylocostal dysostosis, anal and genitourinary malformations and discuss Casamassima-Morton-Nance syndrome.

Published
2007
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31. A new cohort of MECP2 mutation screening in unexplained mental retardation: careful re-evaluation is the best indicator for molecular diagnosis.

Author

Donzel-Javouhey A, Thauvin-Robinet C, Cusin V, Madinier N, Manceau E, Dipanda D, Dulieu V, Mugneret F, Huet F, Teyssier JR, and Faivre L

Subjects
Base Sequence, Cohort Studies, DNA genetics, Female, Genetic Testing, Humans, Male, Phenotype, Rett Syndrome genetics, Intellectual Disability genetics, Methyl-CpG-Binding Protein 2 genetics, Mutation
Published
2006
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32. Molecular analysis of SMA patients without homozygous SMN1 deletions using a new strategy for identification of SMN1 subtle mutations.

Author

Clermont O, Burlet P, Benit P, Chanterau D, Saugier-Veber P, Munnich A, and Cusin V

Subjects
Automation, Chromatography, High Pressure Liquid, Chromosomes, Human, Pair 5 genetics, Haplotypes genetics, Humans, Molecular Sequence Data, Polymerase Chain Reaction, SMN Complex Proteins, Sensitivity and Specificity, Sequence Deletion genetics, Survival of Motor Neuron 1 Protein, Survival of Motor Neuron 2 Protein, Time Factors, Cyclic AMP Response Element-Binding Protein genetics, DNA Mutational Analysis methods, Genetic Testing methods, Homozygote, Muscular Atrophy, Spinal genetics, Mutation genetics, Nerve Tissue Proteins genetics, RNA-Binding Proteins genetics
Abstract

Spinal muscular atrophy (SMA) is a common autosomal recessive disease. SMA is linked to the 5q13 locus in 95% of patients, and in at least 98% of them, the SMN1 homozygous deletion is found. Compound heterozygous patients, who have an SMN1 deletion associated with a subtle mutation, appear undeleted with the common molecular diagnostic test that detects only the homozygous absence of SMN1. In these patients, mutation screening in SMN1 is hampered by the presence of several copies of the highly homologous SMN2 gene. Here, we present a rapid and reliable strategy for detecting SMN mutations using long-range PCR, which avoids cloning and cDNA analysis. Using this method, we found 10 mutations, including five mutations never reported previously and five recurrent mutations; some of them are probably population-specific. Marker analysis of the 5q13 locus in these mutations showed common haplotypes, supporting the hypothesis of a common ancestor rather than a hot spot sequence. We also evaluate the suitability of automated SSCA and DHPLC for mutation scanning., (Copyright 2004 Wiley-Liss, Inc.)

Published
2004
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33. Five years of molecular diagnosis of Fragile X syndrome (1997-2001): a collaborative study reporting 95% of the activity in France.

Author

Biancalana V, Beldjord C, Taillandier A, Szpiro-Tapia S, Cusin V, Gerson F, Philippe C, and Mandel JL

Subjects
Age Factors, Blotting, Southern, Child, Female, France, Genetic Testing methods, Humans, Male, Polymerase Chain Reaction, Sensitivity and Specificity, Sex Factors, Fragile X Syndrome genetics, Genetic Testing statistics & numerical data, Genetic Testing trends
Abstract

The Fragile X syndrome is the most common cause of inherited mental retardation. Clinical features are neither specific nor constant and molecular diagnosis is thus widely used since the characterization of the causal mutation in 1991. The aim of this project was to study the evolution of Fragile X diagnosis in France. A preliminary study of the efficiency of screening for the Fragile X mutation in mentally retarded probands with no previous familial diagnosis was done in the Strasbourg's laboratory with a comparison between data from 1991-1994 and 1997-2000. This study showed an improvement in the use of the Fragile X testing regarding the probands' age at diagnosis and the recruitment of sporadic and female cases. To avoid possible bias in clinical referrals and to evaluate the situation nation wide, this study was enlarged to 28 of the 30 laboratories involved in the Fragile X diagnosis in France from 1997 to 2001 (20,816 probands tested, data representative of 95% of the national screening activity). Median age at diagnosis decreased from 9.2 to 5.8 (average 16-11.6y) between the 1991-1994 and the 1997-2001 studies. Over this period, 477 new families were diagnosed with Fragile X, representing 2.8% of tested male probands (417/14,867) and 1.0% of tested female probands (60/5,949). Forty one percent of positive cases corresponded to probands with a familial history of mental retardation, compared to 66% in the initial (1991-1994) study. We also discuss issues concerning premutations discovered in affected individuals and in females with premature ovarian failure (POF).

Published
2004
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34. Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families.

Author

Viollet L, Zarhrate M, Maystadt I, Estournet-Mathiaut B, Barois A, Desguerre I, Mayer M, Chabrol B, LeHeup B, Cusin V, Billette De Villemeur T, Bonneau D, Saugier-Veber P, Touzery-De Villepin A, Delaubier A, Kaplan J, Jeanpierre M, Feingold J, and Munnich A

Subjects
Chronic Disease, Europe, Family, Female, Founder Effect, Genetic Markers, Humans, Male, Microsatellite Repeats genetics, Pedigree, Recombination, Genetic, Chromosome Mapping, Chromosomes, Human, Pair 11 genetics, Genes, Recessive, Linkage Disequilibrium, Muscular Atrophy, Spinal genetics
Abstract

Chronic distal spinal muscular atrophy (Chronic DSMA, MIM (*)607088) is a rare autosomal recessive disorder characterized by a progressive motor weakness and muscular atrophy, predominating in the distal parts of the limbs. A form of Chronic DSMA gene has been previously mapped to chromosome 11q13 in the 10.3 cM interval defined by loci D11S1889 and D11S1321. By linkage analysis in 12 European Chronic DSMA families, we showed that a disease gene maps to chromosome 11q13.3 (Z(max)=6.66 at theta=0.00 at the DSM4 locus) and suggested that this condition is genetically homogeneous. Recombination events allowed us to reduce the genetic interval to a 2.6 cM region, telomeric to the IGHMBP2 gene, excluding this gene as the disease causing gene in Chronic DSMA. Moreover, partial linkage disequilibrium was found between three rare alleles at loci D11S1369, DSM4 and D11S4184 and the mutant chromosome in European patients. Analysis of the markers at these loci strongly suggests that most Chronic DSMA chromosomes are derived from a single ancestor. Refinement of the Chronic DSMA locus will hopefully allow to test candidate genes and lead to identification of the disease-causing mutations.

Published
2004
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35. Prenatal overgrowth and mosaic trisomy 15q25-qter including the IGF1 receptor gene.

Author

Faivre L, Rousseau T, Laurent N, Gosset P, Sanlaville D, Thauvin-Robinet C, Cusin V, Lionnais S, Callier P, Khau Van Kien P, Huet F, Turleau C, Sagot P, and Mugneret F

Subjects
Abortion, Induced, Adult, Diagnosis, Differential, Female, Humans, Maternal Age, Pregnancy, Pregnancy Trimester, Second, Pregnancy, High-Risk, Trisomy genetics, Trisomy pathology, Chromosomes, Human, Pair 15, Prenatal Diagnosis, Receptor, IGF Type 1 genetics, Trisomy diagnosis
Abstract

Overgrowth is rarely associated with chromosomal imbalances. Here, we report on a male foetus presenting with overgrowth and additional material on the short arm of one of the chromosome 15 in 12% of lymphocytes and 50% of amniotic cells. Parents' karyotypes were normal, indicating a de novo origin for this unbalanced rearrangement. Complementary studies using cytogenetic and FISH studies showed that this additional material resulted in a 15q25-qter trisomy and confirmed the presence of three copies of the insulin-like growth factor 1 receptor (IGF1R) gene, included in the trisomic region. Autopsy performed after termination of pregnancy revealed isolated overgrowth and absence of visceral malformations. The possible mechanisms and origins for the formation of this mosaic pure trisomy are complex. The present observation emphasises the hypothesis that the overgrowth phenotype, frequently reported in patients with trisomy including the 15q26 region, might be causally related to a dosage effect of the IGF1R gene, as well as the importance of chromosome analysis in patients with overgrowth. It also confirms that the overgrowth is of prenatal onset in those observations., (Copyright 2004 John Wiley & Sons, Ltd.)

Published
2004
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36. SHOX point mutations in dyschondrosteosis.

Author

Huber C, Cusin V, Le Merrer M, Mathieu M, Sulmont V, Dagoneau N, Munnich A, and Cormier-Daire V

Subjects
Body Height genetics, Codon, Nonsense genetics, DNA Mutational Analysis, Exons genetics, Frameshift Mutation genetics, Humans, Microsatellite Repeats genetics, Sequence Deletion genetics, Short Stature Homeobox Protein, Homeodomain Proteins genetics, Limb Deformities, Congenital genetics, Point Mutation genetics
Published
2001
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37. Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children.

Author

Malerba G, Lauciello MC, Scherpbier T, Trabetti E, Galavotti R, Cusin V, Pescollderungg L, Zanoni G, Martinati LC, Boner AL, Levitt RC, and Pignatti PF

Subjects
Adult, Bronchial Hyperreactivity genetics, Child, Female, Genetic Predisposition to Disease genetics, Humans, Italy, Male, Phenotype, Asthma genetics, Chromosome Mapping, Chromosomes, Human, Pair 12, Genetic Markers genetics, Respiratory Hypersensitivity genetics
Abstract

We investigated 116 Italian atopic families (560 individuals) for linkage with 13 DNA markers on chromosome 12. All the subjects were phenotyped for asthma, total serum IgE, bronchial hyperresponsiveness, skin-prick positivity to common aeroallergens, and atopy. A relative location map of the markers was prepared from Centre d'Etude du Polymorphisme Humain families. Affected sib pair multipoint linkage methods were used to perform the statistical analyses. We report suggestive linkage for asthma with markers on chromosome 12. The region of interest centers around marker D12S390 (maximum logarithm of odds [mlod] = 2.81; p = 0.003). These results provide additional support that asthma susceptibility factors are located on chromosome 12q.

Published
2000
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38. [Clinical spectrum of prenatal tetralogy of Fallot].

Author

Azancot A, Eydoux P, Vuillard E, Cusin V, Baumann C, and Blot P

Subjects
Abnormalities, Multiple diagnostic imaging, Abnormalities, Multiple embryology, Chromosome Mapping, Female, Fetal Death, Humans, Infant, Newborn, Karyotyping, Pregnancy, Tetralogy of Fallot genetics, Tetralogy of Fallot surgery, Treatment Outcome, Chromosome Aberrations, Echocardiography, Tetralogy of Fallot diagnostic imaging, Tetralogy of Fallot embryology, Ultrasonography, Prenatal
Abstract

The aim of this study of 44 cases of tetralogy of Fallot was to assess the echocardiographic aspects and the prognosis with respect to associated abnormalities and the potential evolution in utero. Group I, tetralogy of Fallot with other abnormalities (N = 27: 2 valvular agenesis, 26.5 5.3 weeks), had genetic anomalies in 18 of the foetus (10 trisomies including 5 trisomy 21, 5 structural abnormalities including 2 micro-deletions 22q11 in the two cases of valvular agenesis, and one deletion of chromosome 8p23.1, 3 mendelian syndromes) and other abnormalities in 9 cases. Hypoplasia of the pulmonary artery was present in 60% of cases with a non-dilated aorta in 72%, infundibular hypertrophy in 33% and 2 evolutions to pulmonary atresia. Aspect of "isolated" ventricular septal defect were observed in 20% of cases. Survival was 10%. In Group II, tetralogy of Fallot was isolated (N = 17, including 2 pulmonary valve agenesis, 31 +/- 6 weeks) (p < 0.01 versus Group I). Pulmonary artery hypoplasia was observed in 50% of cases with dilatation of the aorta and infundibular hypertrophy in all and in one a postnatal progression towards pulmonary atresia. A correlation between growth of the pulmonary artery and gestational age was found in 5 foetus out of 9 studied sequentially (p between 0.03 and 0.007) and between age at first surgery and size of the pulmonary artery (r = 0.80, p = 0.001). Survival was 84%. The risk of malformation (61%) and the prenatal potential evolution of this disease justifies continuous follow-up of all cases of tetralogy of Fallot, high resolution karyotyping and postnatal evaluation in a specialized centre.

Published
2000

39. SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).

Author

Belin V, Cusin V, Viot G, Girlich D, Toutain A, Moncla A, Vekemans M, Le Merrer M, Munnich A, and Cormier-Daire V

Subjects
Female, Genotype, Humans, In Situ Hybridization, Fluorescence, Male, Molecular Sequence Data, Pedigree, Short Stature Homeobox Protein, Translocation, Genetic, X Chromosome, Y Chromosome, Homeodomain Proteins genetics, Mutation, Osteochondrodysplasias genetics
Abstract

Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus.

Published
1998
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