{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:43:46Z","timestamp":1782539026716,"version":"3.54.5"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>A cohort of 542 individuals in 166 families with congenital hearing loss was recruited for whole-exome sequencing analysis. Here, we report the identification of three variants in five affected individuals in two unrelated families. In family 1, a nonsense mutation (c.1516C&amp;gt;T, p.R506*) in the <jats:italic>ATP6V1B2<\/jats:italic> gene, a known causal allele for dominant deafness-onychodystrophy (DDOD), was identified in the mother and son with DDOD. However, a novel heterozygous variant (c.1590T&amp;gt;G, p.D530E) in <jats:italic>TJP2<\/jats:italic>, a known causal gene for hearing-loss, was also detected in the patients. In family 2, the same mutation (c.1516C&amp;gt;T, p.R506*) of <jats:italic>ATP6V1B2<\/jats:italic> was detected from the father and daughter with DDOD. Furthermore, a novel heterozygous variant (c.733A&amp;gt;G, p.M245V) in the <jats:italic>KIF11<\/jats:italic> gene was identified from the spouse with sensorineural hearing-loss and epilepsy. Notably, genotype-phenotype analysis of <jats:italic>KIF11<\/jats:italic>-associated disorders revealed that the p.M245V and two reported hearing-loss-associated variants (p.S235C and p.H244Y) are all mapped to a single \u03b2-sheet (Ser235\u223cM245) in the kinesin motor domain. Together, this is the first demonstration that <jats:italic>ATP6V1B2<\/jats:italic>-caused DDOD is an autosomal dominant genetic disease, compared to previous cases with <jats:italic>de novo<\/jats:italic> mutation. Our findings expand the variant spectrum of hearing-loss-associated genes and provide new insights on understanding of hearing-loss candidate genes <jats:italic>ATP6V1B2<\/jats:italic>, <jats:italic>TJP2<\/jats:italic>, and <jats:italic>KIF11<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fgene.2021.728020","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T13:57:51Z","timestamp":1638367071000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41436-020-00950-9","article-title":"DOORS Syndrome and a Recurrent Truncating ATP6V1B2 Variant","volume":"23","author":"Beauregard-Lacroix","year":"2021","journal-title":"Genet. 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