Yuan Lamei, Guo Yi, Yi Junhui, Xiao Jingjing, Yuan Jinzhong, Xiong Wei, Xu Hongbo, Yang Zhijian, Zhang Jianguo, Deng Hao
*MD †PhD ‡MS §RA Center for Experimental Medicine and Department of Neurology (LY, YG, HX, ZY, HD), Department of Ophthalmology (J Yi), Department of Nephrology (J Yuan), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Medical Information (YG), Cancer Research Institute (WX), Xiangya School of Medicine, Central South University, Changsha, China; and BGI-Shenzhen, Shenzhen, China (JX, JZ).
Optom Vis Sci. 2015 Mar;92(3):337-42. doi: 10.1097/OPX.0000000000000518.
Congenital cataract is a visual impairment that needs correction as early as possible after birth. This study aimed to identify whether genetic defects exist in a Chinese Han pedigree with congenital nuclear cataract.
A family consisting of six members and three patients with nuclear cataract spanning three generations and 100 unrelated ethnically matched normal subjects were recruited in this study. Exome sequencing was performed in the 24-year-old proband, and Sanger sequencing was then conducted in other family members and 100 normal controls.
A novel missense variant, c.428G>A (p.G143E), in the gap junction protein-alpha 3 gene (GJA3) was identified in three patients of the family but unidentified in three family members without lens opacity and 100 normal controls.
A novel missense mutation, c.428G>A (p.G143E), in the GJA3 gene, localized to the cytoplasmic loop, was suggested to be the genetic cause of congenital nuclear cataract, which further expands the gene mutation spectrum. Our findings suggest that exome sequencing is a powerful and cost-effective tool to discover mutation(s) in disorders with high genetic and clinical heterogeneity. Further functional studies in the GJA3 gene mutations may help uncover pathogenic mechanisms of congenital cataract and therefore provide a possible genetic therapy for this disorder.
先天性白内障是一种视力障碍，需要在出生后尽早进行矫正。本研究旨在确定一个中国汉族先天性核性白内障家系中是否存在基因缺陷。
本研究招募了一个由六名成员组成的家系，其中三名患者患有核性白内障，跨越三代，以及100名种族匹配的无关正常受试者。对24岁的先证者进行外显子组测序，然后对其他家庭成员和100名正常对照进行桑格测序。
在家系中的三名患者中鉴定出缝隙连接蛋白α3基因（GJA3）的一个新的错义变体，c.428G>A（p.G143E），但在三名无晶状体混浊的家庭成员和100名正常对照中未鉴定出。
位于细胞质环的GJA3基因中的一个新的错义突变，c.428G>A（p.G143E），被认为是先天性核性白内障的遗传原因，这进一步扩大了基因突变谱。我们的研究结果表明，外显子组测序是发现具有高遗传和临床异质性疾病突变的一种强大且具有成本效益的工具。对GJA3基因突变进行进一步的功能研究可能有助于揭示先天性白内障的致病机制，从而为该疾病提供可能的基因治疗方法。
