Novel mutations in CRYGC are associated with congenital cataracts in Chinese families.
Novel mutations in CRYGC are associated with congenital cataracts in Chinese families.
复制标题
CRYGC的新突变与中国家庭先天性白内障相关
DOI：
10.1038/s41598-017-00318-1
复制
发表时间：
2017-03-15
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Zhong Z;Wu Z;Han L;Chen J
先天性白内障（CC）是导致全球儿童视力丧失的主要原因，约占婴儿失明的三分之一。10-25%的CC病例归因于遗传原因，CC是儿童中临床和遗传高度异质性的透镜疾病。常染色体显性遗传是最常见的遗传方式。本研究从中国15个省、自治区、直辖市共收集了195个无血缘关系的非综合征型ADCC家系。采用桑格测序方法，然后进行家族内共分离，根据美国医学遗传学学院（ACMG）公布的指南进行电子分析和变异解释，以确定遗传缺陷。在两个无关家系中发现的两个突变（p.Tyr139X和p.Ser166Phe）分别与其先天性核性白内障和小角膜相关，这两个突变也是先前报道的。在其他6个先天性核性白内障家系中分别发现了6个新的突变（p.Asp65ThrfsX38、p.Arg142GlyfsX5、p.Arg142AlafsX22、p.Tyr144X、p.Arg169X和p.Tyr46Asp）。在我们的队列中，4.1%的中国ADCC家族是由CD 4GC突变引起的。我们的研究结果扩展了CCLGC突变及其相关表型的谱。
Congenital cataract (CC), responsible for about one-third of blindness in infants, is a major cause of vision loss in children worldwide. 10–25% of CC cases are attributed to genetic causes and CC is a clinically and genetically highly heterogeneous lens disorder in children. Autosomal dominant (AD) inheritance is the most commonly pattern. 195 unrelated non-syndromic ADCC families in this study are recruited from 15 provinces of China. Sanger sequencing approach followed by intra-familial co-segregation, in Silico analyses and interpretation of the variations according to the published guidelines of American College of Medical Genetics (ACMG), were employed to determine the genetic defects. Two mutations (p.Tyr139X and p.Ser166Phe) identified in two unrelated families were associated with their congenital nuclear cataracts and microcornea respectively, which are also reported previously. Six novel CRYGC mutations (p.Asp65ThrfsX38, p.Arg142GlyfsX5, p.Arg142AlafsX22, p.Tyr144X, p.Arg169X, and p.Tyr46Asp) were identified in other six families with congenital nuclear cataracts, respectively. Mutations in the CRYGC were responsible for 4.1% Chinese ADCC families in our cohort. Our results expand the spectrum of CRYGC mutations as well as their associated phenotypes.