Identification of a GJA3 mutation in a Chinese family with congenital nuclear cataract using exome sequencing.
Congenital cataract, a clinically and genetically heterogeneous lens disorder is defined as any opacity of the lens presented from birth and is responsible for approximately 10% of worldwide childhood poor vision or blindness. To identify the genetic defect responsible for congenital nuclear cataract in a four-generation Chinese Han family, exome and direct Sanger sequencings were conducted and a missense variant c.139G>A (p.D47N) in the gap junction protein-alpha 3 gene (GJA3) was identified. The variant co-segregated with patients of the family and was not observed in unaffected family members or normal controls. The above findings indicated that the variant was a pathogenic mutation. The mutation p.D47N was found in the first extracellular loop (El) domain of GJA3 protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in cataract, a disorder with high genetic heterogeneity. Our findings may also provide new insights into the cause and diagnosis of congenital nuclear cataract and have implications for genetic counseling.
Yi
Y
Guo
Lamei
L
Yuan
Junhui
J
Yi
Jingjing
J
Xiao
Hongbo
H
Xu
Hongwei
H
Lv
Wei
W
Xiong
Wen
W
Zheng
Liping
L
Guan
Jianguo
J
Zhang
Hong
H
Xiang
Yong
Y
Qi
Hao
H
Deng
D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002417:Cattle; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
D017630:Connexins; C082917:GJA3 protein, human