title: A novel GJA3 mutation associated with congenital nuclear pulverulent and posterior polar cataract in a Chinese family.
abstract: Congenital cataract (CC) is the leading cause of visual disability in children. To date, mutations in many genes have been linked to CC. In a four-generation Chinese family with congenital nuclear pulverulent and posterior polar cataracts, we detected a heterozygous c.5G>A transition in the second exon of GJA3, resulting in the substitution of a highly conserved glycine with aspartic acid (p.G2D) at the N-terminus of the connexin46 (Cx46) protein. Wild type (wt) and mutant Cx46 plasmids were transfected into HeLa cells to examine the molecular basis of cataract formation. Unlike wt Cx46, Cx46G2D mutant formed gap junction plaques inefficiently, changed hemichannel permeability, and caused apoptosis. These results suggest that the glycine residue at the second position of the N-terminus is important for gap junction plaque formation and hemichannel function.
authors.affiliation: Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China. xlren@zju.edu.cn
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chongfei
authors.initials: C
authors.lastname: Jin
authors.forename: Xingchao
authors.initials: X
authors.lastname: Shentu
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Ni
mesh_terms: D017209:Apoptosis; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D017630:Connexins / Q000235:genetics*; D005190:Family; D005260:Female; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D017630:Connexins; C082917:GJA3 protein, human