Zhou Yu, Zhai Yaru, Huang Lulin, Gong Bo, Li Jie, Hao Fang, Wu Zhengzheng, Shi Yi, Yang Yin
Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Center of Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China.
Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
J Ophthalmol. 2016;2016:4353957. doi: 10.1155/2016/4353957. Epub 2016 Nov 29.
Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T<G (p.E167X) in gene was found. And the results showed that the mutation cosegregated with the disease phenotype in the family and was absolutely absent in 1000 ethnicity-matched control samples. Thus, the heterozygous mutation c.499T<G (p.E167X) in was the causal mutation responsible for this ADCC family. In conclusion, our findings revealed a novel stopgain mutation c.499T<G (p.E167X) in the exon 6 of which expanded the mutation spectrum of in Chinese congenital cataract population and illustrated the important role of in the genetics research of congenital cataract.
先天性白内障是儿童视力残疾和失明的最常见原因。本研究旨在利用新一代测序技术，在中国一个家族中鉴定常染色体显性先天性白内障（ADCC）的基因突变。该家族包括8名未受影响个体和5名受影响个体。在进行全面的眼科检查后，采集了先证者和两名可获得的家族成员的血样。然后对先证者进行全外显子组测序，并应用桑格测序法验证两名家族成员和对照样本中的致病突变。在通过一系列现有变异数据库对全外显子组测序数据进行筛选后，发现基因中存在一个杂合突变c.499T<G（p.E167X）。结果表明，该突变与家族中的疾病表型共分离，在1000例种族匹配的对照样本中完全不存在。因此，基因中的杂合突变c.499T<G（p.E167X）是导致这个ADCC家族发病的致病突变。总之，我们的研究结果揭示了基因外显子6中一个新的截短突变c.499T<G（p.E167X），这扩展了中国先天性白内障人群中该基因的突变谱，并说明了该基因在先天性白内障遗传学研究中的重要作用。
