{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:13:07Z","timestamp":1787501587348,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Finnish Foundation for Ear Diseases"},{"name":"Emil Aaltonen Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The objective was to study the genetic etiology of M\u00e9ni\u00e8re\u2019s disease (MD) using next-generation sequencing in three families with three cases of MD. Whole exome sequencing was used to identify rare genetic variants co-segregating with MD in Finnish families. In silico estimations and population databases were used to estimate the frequency and pathogenicity of the variants. Variants were validated and genotyped from additional family members using capillary sequencing. A geneMANIA analysis was conducted to investigate the functional pathways and protein interactions of candidate genes. Seven rare variants were identified to co-segregate with MD in the three families: one variant in the CYP2B6 gene in family I, one variant in GUSB and EPB42 in family II, and one variant in each of the SLC6A, ASPM, KNTC1, and OVCH1 genes in family III. Four of these genes were linked to the same co-expression network with previous familial MD candidate genes. Dysfunction of CYP2B6 and SLC6A could predispose to MD via the oxidative stress pathway. Identification of ASPM and KNTC1 as candidate genes for MD suggests dysregulation of mitotic spindle formation in familial MD. The genetic etiology of familial MD is heterogenic. Our findings suggest a role for genes acting on oxidative stress and mitotic spindle formation in MD but also highlight the genetic complexity of MD.<\/jats:p>","DOI":"10.3390\/genes13060998","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T12:48:31Z","timestamp":1654087711000},"page":"998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["New Genetic Variants in CYP2B6 and SLC6A Support the Role of Oxidative Stress in Familial M\u00e9ni\u00e8re\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-4221","authenticated-orcid":false,"given":"Sini","family":"Skarp","sequence":"first","affiliation":[{"name":"Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Korvala","sequence":"additional","affiliation":[{"name":"University of Oulu Graduate School, University of Oulu, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouko","family":"Kotim\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Kainuu Central Hospital, 87300 Kajaani, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martti","family":"Sorri","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University Hospital, 90220 Oulu, Finland"},{"name":"Finland & PEDEGO Research Unit, University of Oulu, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"M\u00e4nnikk\u00f6","sequence":"additional","affiliation":[{"name":"Infrastructure for Population Studies, Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Hietikko","sequence":"additional","affiliation":[{"name":"Center for Life-Course Health Research, Faculty of Medicine, University of Oulu, Finland and Oulu City Hospital, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"ref_1","first-page":"23102312","article-title":"ber die Pathologische Ver\u00e4nderung bei einem Meniere-Kranken","volume":"44","author":"Yamakawa","year":"1938","journal-title":"J. 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