A novel mutation in the connexin 46 (GJA3) gene associated with autosomal dominant congenital cataract in an Indian family.
OBJECTIVE
To identify the genetic defect in an autosomal dominant congenital cataract family (ADCC), having 18 individuals in four generations affected with embryonal cataract.


METHODS
A genome wide scan using the GeneChip Human Mapping 10K Array, version 2 was performed on DNA samples from eight affected and two unaffected members of an ADCC family having 18 members in four generations affected with embryonal cataract. The region of potential linkage delimited by single nucleotide polymorphic (SNP) markers was analyzed using fluorescently labeled microsatellite markers. Mutation screening was performed in the candidate gene by bidirectional sequencing of amplified products.


RESULTS
By whole genome screening linkage in this family, the genetic defect was located to a region of chromosome 13q11 which contains the candidate gene connexin 46 (GJA3) for ADCC. Sequencing of the coding region of GJA3 showed a novel heterozygous 98G>T change resulting in the substitution of highly conserved arginine by leucine at codon 33 (R33L), located in the first transmembrane domain of GJA3. This nucleotide change was not seen in any unaffected members of this family nor in 50 unrelated control subjects.


CONCLUSIONS
The present study describes a novel mutation (R33L) in the GJA3 associated with finely granular embryonal cataract. These findings expand the mutation spectrum of GJA3 in association with congenital cataract.
Guleria
Kamlesh
K
Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India.
Sperling
Karl
K
Singh
Daljit
D
Varon
Raymonda
R
Singh
Jai Rup
JR
Vanita
Vanita
V
D019943:Amino Acid Substitution; D001120:Arginine; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D017630:Connexins; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006147:Guanine; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007194:India; D007930:Leucine; D008126:Lod Score; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013941:Thymine
D017630:Connexins; C082917:GJA3 protein, human; D006147:Guanine; D001120:Arginine; D007930:Leucine; D013941:Thymine