Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype-Phenotype Correlations in 27 Chinese Han Families.
Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype-Phenotype Correlations in 27 Chinese Han Families.
复制标题
先天性白内障相关基因的靶向外显子组测序：拓宽27个中国汉族家系的突变谱和基因型-表型相关性
DOI：
10.1038/s41598-017-01182-9
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发表时间：
2017-04-27
影响因子：
4.6
通讯作者：
Yao K
中科院分区：
文献类型：
--
作者：
Zhai Y;Li J;Yu W;Zhu S;Yu Y;Wu M;Sun G;Gong X;Yao K
先天性白内障是最常见的遗传性眼病，也是导致终生视力丧失的最主要原因。在某些情况下，对致病基因突变的筛选可能非常具有挑战性，因为先天性白内障是临床和遗传上的异质性疾病。本研究的目的是调查27个中国先天性白内障家系中54个白内障相关基因的突变谱和频率。通过靶向下一代测序(NGS)筛选了54个白内障相关基因的变异，然后通过Sanger测序进行了验证。我们在62.96%(17/27)的家系中发现了致病变异，其中52.94%(9/17)以上的变异是新的。其中3个为剪接位点突变，4个为无义突变，7个为错义突变，2个为移码突变，1个为内含子突变。这包括鉴定：由两个新的PAX6突变引起的复杂的眼部表型；由两个新的CRYGS突变引起的进行性皮质性白内障和伴有晶状体半脱位的板层白内障。罕见的基因突变还包括CRYBA4、CRYBA2、BFSP1、VIM、HSF4和EZR。我们的研究扩大了导致先天性白内障的基因的突变范围和频率。遗传性先天性白内障患者的靶向下一代测序提供了重要的诊断信息。
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.