Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy

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>T, p.R506*) in the...

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Autores principales:	Yuan Li, Jianjun Xiong, Yi Zhang, Lin Xu, Jianyun Liu, Tao Cai
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	DDOD (dominant deafness-onychodystrophy) hearing loss whole-exome sequencing (WES) ATP6V1B2 TJP2 KIF11 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/74237a4fdd4e4430b6c68aeee0887044
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spelling	oai:doaj.org-article:74237a4fdd4e4430b6c68aeee08870442021-12-01T13:57:37ZCase Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy1664-802110.3389/fgene.2021.728020https://doaj.org/article/74237a4fdd4e4430b6c68aeee08870442021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.728020/fullhttps://doaj.org/toc/1664-8021A 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>T, p.R506) in the ATP6V1B2 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>G, p.D530E) in TJP2, a known causal gene for hearing-loss, was also detected in the patients. In family 2, the same mutation (c.1516C>T, p.R506) of ATP6V1B2 was detected from the father and daughter with DDOD. Furthermore, a novel heterozygous variant (c.733A>G, p.M245V) in the KIF11 gene was identified from the spouse with sensorineural hearing-loss and epilepsy. Notably, genotype-phenotype analysis of KIF11-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 β-sheet (Ser235∼M245) in the kinesin motor domain. Together, this is the first demonstration that ATP6V1B2-caused DDOD is an autosomal dominant genetic disease, compared to previous cases with de novo mutation. Our findings expand the variant spectrum of hearing-loss-associated genes and provide new insights on understanding of hearing-loss candidate genes ATP6V1B2, TJP2, and KIF11.Yuan LiJianjun XiongJianjun XiongJianjun XiongYi ZhangLin XuJianyun LiuTao CaiFrontiers Media S.A.articleDDOD (dominant deafness-onychodystrophy)hearing losswhole-exome sequencing (WES)ATP6V1B2TJP2KIF11GeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DDOD (dominant deafness-onychodystrophy) hearing loss whole-exome sequencing (WES) ATP6V1B2 TJP2 KIF11 Genetics QH426-470
spellingShingle	DDOD (dominant deafness-onychodystrophy) hearing loss whole-exome sequencing (WES) ATP6V1B2 TJP2 KIF11 Genetics QH426-470 Yuan Li Jianjun Xiong Jianjun Xiong Jianjun Xiong Yi Zhang Lin Xu Jianyun Liu Tao Cai Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
description	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>T, p.R506) in the ATP6V1B2 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>G, p.D530E) in TJP2, a known causal gene for hearing-loss, was also detected in the patients. In family 2, the same mutation (c.1516C>T, p.R506) of ATP6V1B2 was detected from the father and daughter with DDOD. Furthermore, a novel heterozygous variant (c.733A>G, p.M245V) in the KIF11 gene was identified from the spouse with sensorineural hearing-loss and epilepsy. Notably, genotype-phenotype analysis of KIF11-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 β-sheet (Ser235∼M245) in the kinesin motor domain. Together, this is the first demonstration that ATP6V1B2-caused DDOD is an autosomal dominant genetic disease, compared to previous cases with de novo mutation. Our findings expand the variant spectrum of hearing-loss-associated genes and provide new insights on understanding of hearing-loss candidate genes ATP6V1B2, TJP2, and KIF11.
format	article
author	Yuan Li Jianjun Xiong Jianjun Xiong Jianjun Xiong Yi Zhang Lin Xu Jianyun Liu Tao Cai
author_facet	Yuan Li Jianjun Xiong Jianjun Xiong Jianjun Xiong Yi Zhang Lin Xu Jianyun Liu Tao Cai
author_sort	Yuan Li
title	Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
title_short	Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
title_full	Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
title_fullStr	Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
title_full_unstemmed	Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy
title_sort	case report: exome sequencing identified variants in three candidate genes from two families with hearing loss, onychodystrophy, and epilepsy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/74237a4fdd4e4430b6c68aeee0887044
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Case Report: Exome Sequencing Identified Variants in Three Candidate Genes From Two Families With Hearing Loss, Onychodystrophy, and Epilepsy

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