title: Identification of a novel GJA3 mutation in congenital nuclear cataract.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: *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).
authors: Lamei
authors: L
authors: Yuan
authors: Yi
authors: Y
authors: Guo
authors: Junhui
authors: J
authors: Yi
authors: Jingjing
authors: J
authors: Xiao
authors: Jinzhong
authors: J
authors: Yuan
authors: Wei
authors: W
authors: Xiong
authors: Hongbo
authors: H
authors: Xu
authors: Zhijian
authors: Z
authors: Yang
authors: Jianguo
authors: J
authors: Zhang
authors: Hao
authors: H
authors: Deng
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002386:Cataract / Q000151:congenital* / Q000235:genetics; D002681:China; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D017630:Connexins; C082917:GJA3 protein, human