{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:01Z","timestamp":1777680001857,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["BR-GE-0120-0775-LUMC"],"award-info":[{"award-number":["BR-GE-0120-0775-LUMC"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Usher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the most severe form, and type II, the most frequent form, respectively. Massively parallel sequencing was performed on a cohort of patients in the context of a molecular diagnosis to confirm clinical suspicion of Usher syndrome. We report here 231 pathogenic MYO7A and USH2A genotypes identified in 73 Usher type I and 158 Usher type II patients. Furthermore, we present the ACMG classification of the variants, which comprise all types. Among them, 68 have not been previously reported in the literature, including 12 missense and 16 splice variants. We also report a new deep intronic variant in USH2A. Despite the important number of molecular studies published on these two genes, we show that during the course of routine genetic diagnosis, undescribed variants continue to be identified at a high rate. This is particularly pertinent in the current era, where therapeutic strategies based on DNA or RNA technologies are being developed.<\/jats:p>","DOI":"10.3390\/ijms222413294","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T08:17:58Z","timestamp":1639124278000},"page":"13294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-0994","authenticated-orcid":false,"given":"Luke","family":"Mansard","sequence":"first","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-1221","authenticated-orcid":false,"given":"David","family":"Baux","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, Inserm, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-9139","authenticated-orcid":false,"given":"Christel","family":"Vach\u00e9","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, Inserm, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Blanchet","sequence":"additional","affiliation":[{"name":"National Reference Centre for Inherited Sensory Diseases, University Montpellier, CHU Montpellier, F-34000 Montpellier, France"},{"name":"Oto Laryngology Department, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Meunier","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, Inserm, F-34000 Montpellier, France"},{"name":"National Reference Centre for Inherited Sensory Diseases, University Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, Inserm, F-34000 Montpellier, France"},{"name":"Medical Genetics Department, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Faug\u00e8re","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Baudoin","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melody","family":"Moclyn","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene","family":"Dollfus","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Affections in Ophthalmology Genetics (CARGO), Institute of Medical Genetics of Alsace, University of Strasbourg, CHU Strasbourg, F-67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Gilbert-Dussardier","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, University of Poitiers, CHU Poitiers, F-86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Dupin-Deguine","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, University of Toulouse, CHU Purpan, F-31000 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Bonneau","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, University of Angers, CHU Angers, F-49000 Angers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Drumare","sequence":"additional","affiliation":[{"name":"Vision and Neuro-Ophthalmology Department, University of Lille, CHU Lille, F-59000 Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Odent","sequence":"additional","affiliation":[{"name":"Clinical Genetics Service, University Hospital, Genetics and Development Institute of Rennes IDGDR, UMR6290 University of Rennes, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Zanlonghi","sequence":"additional","affiliation":[{"name":"Center of Competence for Rare Diseases, Jules Verne Clinic, F-44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Claustres","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Koenig","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-8807","authenticated-orcid":false,"given":"Vasiliki","family":"Kalatzis","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, Inserm, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5914-2335","authenticated-orcid":false,"given":"Anne-Fran\u00e7oise","family":"Roux","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, University of Montpellier, CHU Montpellier, F-34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), University of Montpellier, Inserm, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"An Update on the Genetics of Usher Syndrome","volume":"2011","author":"Aller","year":"2011","journal-title":"J. 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