Congenital anterior polar cataract associated with a missense mutation in the human alpha crystallin gene CRYAA.

Purpose: To identify the potential pathogenic mutation over four generations of a Chinese family with congenital anterior polar cataracts (APC).

Methods: We investigated four generations of a Chinese family who are afflicted with anterior polar cataracts. The family resides in a relatively isolated region of Northern China. Peripheral blood samples were collected from all of the family members, and genomic DNA was then extracted from the blood samples. A gene scan was performed using about 400 primers labeled with fluorescent stain. Linkage software defined the region of the diseased gene with a Linkage analysis, and Cyrillic software processed the resulting haplotypes. Mutation detection was performed in the candidate gene by sequencing amplified products.

Results: A maximum logarithm of odds score (LOD) score was obtained at marker D21S1252(LOD score [Z]=3.23, recombination fraction [θ]=0.0. Haplotype analysis traced the disease gene to an 18.47 cM region bounded by D21S263 and D21S266 on chromosome21q22.11-q22.3. Direct sequencing of the candidate alpha A crystallin (CRYAA) gene revealed a c.347G>A transition in exon 3 of CRYAA that co-segregated with the cataract in the family members and was not observed in 100 control patients. This single-nucleotide change resulted in the substitution of a highly conserved Arginine by Histidine (R116H).

Conclusions: The present study identified a missense mutation (R116H) in the CRYAA gene that causes autosomal dominant congenital anterior polar cataracts in a Chinese family. Our finding confirms the high rate of apparently independent mutations at this dinucleotide.