A novel mutation in the connexin 46 (GJA3) gene associatedwith autosomal dominant congenital cataract in an Indian family

[摘要] Purpose: To identify the genetic defect in an autosomal dominantcongenital cataract family (ADCC), having 18 individuals in fourgenerations affected with embryonal cataract.Methods: A genome wide scan using the GeneChip Human Mapping 10KArray, version 2 was performed on DNA samples from eight affected andtwo unaffected members of an ADCC family having 18 members in fourgenerations affected with embryonal cataract. The region of potentiallinkage delimited by single nucleotide polymorphic (SNP) markers wasanalyzed using fluorescently labeled microsatellite markers. Mutationscreening was performed in the candidate gene by bidirectionalsequencing of amplified products.Results: By whole genome screening linkage in this family, thegenetic defect was located to a region of chromosome 13q11 whichcontains the candidate gene connexin 46 (GJA3) for ADCC.Sequencing of the coding region of GJA3 showed a novel heterozygous98G>T change resulting in the substitution of highly conservedarginine by leucine at codon 33 (R33L), located in the firsttransmembrane domain of GJA3. This nucleotide change was not seen inany unaffected members of this family nor in 50 unrelated controlsubjects.Conclusions: The present study describes a novel mutation (R33L) inthe GJA3 associated with finely granular embryonal cataract. Thesefindings expand the mutation spectrum of GJA3 in association withcongenital cataract.

[学科分类] 生物化学/生物物理