A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss

Abstract Autosomal dominant non-syndromic hearing loss (ADNSHL) is genetically heterogeneous with more than 35 genes identified to date. Using a massively parallel sequencing panel targeting 159 deafness genes, we identified a novel missense variant of POU4F3 (c.982A>G, p.Lys328Glu) which co-segr...

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Autores principales:	Yin-Hung Lin, Yi-Hsin Lin, Ying-Chang Lu, Tien-Chen Liu, Chien-Yu Chen, Chuan-Jen Hsu, Pei-Lung Chen, Chen-Chi Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fd3b4a931d784852b7b020b70eade438
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spelling	oai:doaj.org-article:fd3b4a931d784852b7b020b70eade4382021-12-02T15:05:59ZA novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss10.1038/s41598-017-08236-y2045-2322https://doaj.org/article/fd3b4a931d784852b7b020b70eade4382017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08236-yhttps://doaj.org/toc/2045-2322Abstract Autosomal dominant non-syndromic hearing loss (ADNSHL) is genetically heterogeneous with more than 35 genes identified to date. Using a massively parallel sequencing panel targeting 159 deafness genes, we identified a novel missense variant of POU4F3 (c.982A>G, p.Lys328Glu) which co-segregated with the deafness phenotype in a three-generation Taiwanese family with ADNSHL. This variant could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. We then performed subcellular localization experiments and confirmed that p.Lys328Glu compromised transportation of POU4F3 from the cytoplasm to the nucleus. POU3F4 p.Lys328Glu was located within a bipartite nuclear localization signal (NLS), and was the first missense variant in bipartite NLS of POU4F3 validated in functional studies. These findings expanded the mutation spectrum of POU4F3 and provided insight into the pathogenesis associated with aberrant POU4F3 localization.Yin-Hung LinYi-Hsin LinYing-Chang LuTien-Chen LiuChien-Yu ChenChuan-Jen HsuPei-Lung ChenChen-Chi WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yin-Hung Lin Yi-Hsin Lin Ying-Chang Lu Tien-Chen Liu Chien-Yu Chen Chuan-Jen Hsu Pei-Lung Chen Chen-Chi Wu A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss
description	Abstract Autosomal dominant non-syndromic hearing loss (ADNSHL) is genetically heterogeneous with more than 35 genes identified to date. Using a massively parallel sequencing panel targeting 159 deafness genes, we identified a novel missense variant of POU4F3 (c.982A>G, p.Lys328Glu) which co-segregated with the deafness phenotype in a three-generation Taiwanese family with ADNSHL. This variant could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. We then performed subcellular localization experiments and confirmed that p.Lys328Glu compromised transportation of POU4F3 from the cytoplasm to the nucleus. POU3F4 p.Lys328Glu was located within a bipartite nuclear localization signal (NLS), and was the first missense variant in bipartite NLS of POU4F3 validated in functional studies. These findings expanded the mutation spectrum of POU4F3 and provided insight into the pathogenesis associated with aberrant POU4F3 localization.
format	article
author	Yin-Hung Lin Yi-Hsin Lin Ying-Chang Lu Tien-Chen Liu Chien-Yu Chen Chuan-Jen Hsu Pei-Lung Chen Chen-Chi Wu
author_facet	Yin-Hung Lin Yi-Hsin Lin Ying-Chang Lu Tien-Chen Liu Chien-Yu Chen Chuan-Jen Hsu Pei-Lung Chen Chen-Chi Wu
author_sort	Yin-Hung Lin
title	A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss
title_short	A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss
title_full	A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss
title_fullStr	A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss
title_full_unstemmed	A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss
title_sort	novel missense variant in the nuclear localization signal of pou4f3 causes autosomal dominant non-syndromic hearing loss
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fd3b4a931d784852b7b020b70eade438
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A novel missense variant in the nuclear localization signal of POU4F3 causes autosomal dominant non-syndromic hearing loss

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