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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

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...

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Published in:Scientific reports 2017-04, Vol.7 (1), p.1219-9, Article 1219
Main Authors: Zhai, Yi, Li, Jinyu, Yu, Wangshu, Zhu, Sha, Yu, Yinhui, Wu, Menghan, Sun, Guizhen, Gong, Xiaohua, Yao, Ke
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description 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.
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subjects 45
45/23
631/208/2489/144
692/699/3161/3168
Alleles
Asian Continental Ancestry Group
Cataract - congenital
Cataract - genetics
Cataracts
Cortex
Exome
Family Health
Gene frequency
Genetic Association Studies
Genotype
High-Throughput Nucleotide Sequencing
Humanities and Social Sciences
Humans
Missense mutation
multidisciplinary
Mutation
Pax6 protein
Science
Science (multidisciplinary)
Splicing
title 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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