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

  • 24 October 2003
    • journal article
    • Vol. 9, 579-83
Abstract
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. 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. 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. 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.

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