Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families

Abstract Congenital cataract is the most frequent inherited ocular disorder and the most leading cause of lifelong visual loss. The screening of pathogenic mutations can be very challenging in some cases, for congenital cataracts are clinically and genetically heterogeneous diseases. The aim of this...

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Autores principales:	Yi Zhai, Jinyu Li, Wangshu Yu, Sha Zhu, Yinhui Yu, Menghan Wu, Guizhen Sun, Xiaohua Gong, Ke Yao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b91ec7334f13432abe52e7c4701bfb5d
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spelling	oai:doaj.org-article:b91ec7334f13432abe52e7c4701bfb5d2021-12-02T11:52:37ZTargeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families10.1038/s41598-017-01182-92045-2322https://doaj.org/article/b91ec7334f13432abe52e7c4701bfb5d2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01182-9https://doaj.org/toc/2045-2322Abstract Congenital cataract is the most frequent inherited ocular disorder and the most leading cause of lifelong visual loss. The screening of pathogenic mutations can be very challenging in some cases, for congenital cataracts are clinically and genetically heterogeneous diseases. The aim of this study is to investigate the mutation spectrum and frequency of 54 cartaract-associated genes in 27 Chinese families with congenital cataracts. Variants in 54 cataract-associated genes were screened by targeted next-generation sequencing (NGS) and then validated by Sanger sequencing. We identified pathogenic variants in 62.96% (17/27) of families, and over 52.94% (9/17) of these variants were novel. Among them, three are splicing site mutations, four are nonsense mutations, seven are missense mutations, two are frame shift mutations and one is intronic mutation. This included identification of: complex ocular phenotypes due to two novel PAX6 mutations; progressive cortical cataract and lamellar cataract with lens subluxation due to two novel CRYGS mutations. Mutations were also found in rarely reported genes including CRYBA4, CRYBA2, BFSP1, VIM, HSF4, and EZR. Our study expands the mutation spectrum and frequency of genes responsible for congenital cataracts. Targeted next-generation sequencing in inherited congenital cataract patients provided significant diagnostic information.Yi ZhaiJinyu LiWangshu YuSha ZhuYinhui YuMenghan WuGuizhen SunXiaohua GongKe YaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi Zhai Jinyu Li Wangshu Yu Sha Zhu Yinhui Yu Menghan Wu Guizhen Sun Xiaohua Gong Ke Yao Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families
description	Abstract Congenital cataract is the most frequent inherited ocular disorder and the most leading cause of lifelong visual loss. The screening of pathogenic mutations can be very challenging in some cases, for congenital cataracts are clinically and genetically heterogeneous diseases. The aim of this study is to investigate the mutation spectrum and frequency of 54 cartaract-associated genes in 27 Chinese families with congenital cataracts. Variants in 54 cataract-associated genes were screened by targeted next-generation sequencing (NGS) and then validated by Sanger sequencing. We identified pathogenic variants in 62.96% (17/27) of families, and over 52.94% (9/17) of these variants were novel. Among them, three are splicing site mutations, four are nonsense mutations, seven are missense mutations, two are frame shift mutations and one is intronic mutation. This included identification of: complex ocular phenotypes due to two novel PAX6 mutations; progressive cortical cataract and lamellar cataract with lens subluxation due to two novel CRYGS mutations. Mutations were also found in rarely reported genes including CRYBA4, CRYBA2, BFSP1, VIM, HSF4, and EZR. Our study expands the mutation spectrum and frequency of genes responsible for congenital cataracts. Targeted next-generation sequencing in inherited congenital cataract patients provided significant diagnostic information.
format	article
author	Yi Zhai Jinyu Li Wangshu Yu Sha Zhu Yinhui Yu Menghan Wu Guizhen Sun Xiaohua Gong Ke Yao
author_facet	Yi Zhai Jinyu Li Wangshu Yu Sha Zhu Yinhui Yu Menghan Wu Guizhen Sun Xiaohua Gong Ke Yao
author_sort	Yi Zhai
title	Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families
title_short	Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families
title_full	Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families
title_fullStr	Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families
title_full_unstemmed	Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families
title_sort	targeted exome sequencing of congenital cataracts related genes: broadening the mutation spectrum and genotype–phenotype correlations in 27 chinese han families
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b91ec7334f13432abe52e7c4701bfb5d
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Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families

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