A novel mutation in GJA3 (connexin46) for autosomal dominant congenital nuclear pulverulent cataract.

PURPOSE: Autosomal dominant congenital cataract (ADCC) is a clinically and genetically heterogeneous lens disorder that usually presents as a sight-threatening trait in childhood. Here, we described a six-generation Chinese family presenting with morphologically homogeneous "nuclear pulverulent" cataracts.
METHODS: A whole genome scan was performed with polymorphic microsatellites in the Human MapPairs marker set, with special attention paid to known ADCC loci. Then we screened for mutations by direct sequencing.
RESULTS: A significantly positive two-point LOD score was obtained at marker D13S175(Zmax=7.83, theta=0). Haplotype analysis indicated this disease was located at 13q11, close to GJA3. Upon screening for mutations in GJA3 in this family, we found a novel transition mutation (TTC->TTA) resulting in a Phenylalanine-Leucine substitution at the highly conserved codon 32 of the GJA3 protein. This mutation segregated with the affected members of the family.
CONCLUSIONS: This finding is the first report of a mutation in the first transmembrane region of GJA3. Our study further confirmed that GJA3 plays a vital role in the maintenance of human lens transparency.