{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:43:03Z","timestamp":1792024983851,"version":"4.4.0"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center, Poland","doi-asserted-by":"publisher","award":["2021\/41\/B\/NZ5\/04390"],"award-info":[{"award-number":["2021\/41\/B\/NZ5\/04390"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute of Physiology and Pathology of Hearing","award":["2021\/41\/B\/NZ5\/04390"],"award-info":[{"award-number":["2021\/41\/B\/NZ5\/04390"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause of inner ear malformation but the genetics still needs clarification. The aim of this study was to identify the cause of EVA in patients with hearing loss (HL). Genomic DNA was isolated from HL patients with radiologically confirmed bilateral EVA (n = 23) and analyzed by next generation sequencing using a custom HL gene panel encompassing 237 HL-related genes or a clinical exome. The presence and segregation of selected variants and the CEVA haplotype (in the 5\u2032 region of SLC26A4) was verified by Sanger sequencing. Minigene assay was used to evaluate the impact of novel synonymous variant on splicing. Genetic testing identified the cause of EVA in 17\/23 individuals (74%). Two pathogenic variants in the SLC26A4 gene were identified as the cause of EVA in 8 of them (35%), and a CEVA haplotype was regarded as the cause of EVA in 6 of 7 patients (86%) who carried only one SLC26A4 genetic variant. In two individuals with a phenotype matching branchio-oto-renal (BOR) spectrum disorder, cochlear hypoplasia resulted from EYA1 pathogenic variants. In one patient, a novel variant in CHD7 was detected. Our study shows that SLC26A4, together with the CEVA haplotype, accounts for more than half of EVA cases. Syndromic forms of HL should also be considered in patients with EVA. We conclude that to better understand inner ear development and the pathogenesis of its malformations, there is a need to look for pathogenic variants in noncoding regions of known HL genes or to link them with novel candidate HL genes.<\/jats:p>","DOI":"10.3390\/genes14020335","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T06:06:13Z","timestamp":1675058773000},"page":"335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Genetic Background of Hearing Loss in Patients with EVA and Cochlear Malformation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-8821","authenticated-orcid":false,"given":"Natalia","family":"Ba\u0142dyga","sequence":"first","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"},{"name":"Doctoral School of Translational Medicine, Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-8002","authenticated-orcid":false,"given":"Dominika","family":"Ozi\u0119b\u0142o","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"},{"name":"Doctoral School of Translational Medicine, Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Furmanek","sequence":"additional","affiliation":[{"name":"Bioimaging Research Center, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-8377","authenticated-orcid":false,"given":"Marcin L.","family":"Leja","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-9851","authenticated-orcid":false,"given":"Henryk","family":"Skar\u017cy\u0144ski","sequence":"additional","affiliation":[{"name":"Oto-Rhino-Laryngology Surgery Clinic, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-9141","authenticated-orcid":false,"given":"Monika","family":"O\u0142dak","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/cii.416","article-title":"Cochlear implantation in inner ear malformations\u2014A review article","volume":"11","author":"Sennaroglu","year":"2010","journal-title":"Cochlear Implant. 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