{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:52:49Z","timestamp":1770461569475,"version":"3.49.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>GSDME, also known as DFNA5, is a gene implicated in autosomal dominant nonsyndromic hearing loss (ADNSHL), affecting, at first, the high frequencies with a subsequent progression over all frequencies. To date, all the GSDME pathogenic variants associated with deafness lead to skipping of exon 8. In two families with apparent ADNSHL, massively parallel sequencing (MPS) integrating a coverage-based method for detection of copy number variations (CNVs) was applied, and it identified the first two causal GSDME structural variants affecting exon 8. The deleterious impact of the c.991-60_1095del variant, which includes the acceptor splice site sequence of exon 8, was confirmed by the study of the proband\u2019s transcripts. The second mutational event is a complex rearrangement that deletes almost all of the exon 8 sequence. This study increases the mutational spectrum of the GSDME gene and highlights the crucial importance of MPS data for the detection of GSDME exon 8 deletions, even though the identification of a causal single-exon CNV by MPS analysis is still challenging.<\/jats:p>","DOI":"10.3390\/diagnostics12010207","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of the First Single GSDME Exon 8 Structural Variants Associated with Autosomal Dominant Hearing Loss"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-0994","authenticated-orcid":false,"given":"Luke","family":"Mansard","sequence":"first","affiliation":[{"name":"Molecular Genetics Laboratory, Univ Montpellier, CHU Montpellier, 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, Univ Montpellier, CHU Montpellier, 34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), Univ Montpellier, Inserm, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, Univ Montpellier, CHU Montpellier, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Baudoin","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, Univ Montpellier, CHU Montpellier, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-6180","authenticated-orcid":false,"given":"Isabelle","family":"Perthus","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Reference Center for Rare Diseases, University Hospital of Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, CHU Nantes, 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Blanchet","sequence":"additional","affiliation":[{"name":"National Reference Centre for Inherited Sensory Diseases, Otolaryngology Department, Univ Montpellier, CHU Montpellier, 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, Univ Montpellier, CHU Montpellier, 34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), Univ Montpellier, Inserm, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Koenig","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, Univ Montpellier, CHU Montpellier, 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), Univ Montpellier, Inserm, 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, Univ Montpellier, CHU Montpellier, 34000 Montpellier, France"},{"name":"Institute for Neurosciences of Montpellier (INM), Univ Montpellier, Inserm, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/ejhg.2011.63","article-title":"The DFNA5 Gene, Responsible for Hearing Loss and Involved in Cancer, Encodes a Novel Apoptosis-Inducing Protein","volume":"19","author":"Thys","year":"2011","journal-title":"Eur. 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