Purpose: To report the recurrent p.R116H mutation in the αA-crystallin gene (CRYAA) which causes a novel variable cataract phenotype, and to determine whether this mutation represents a mutational hot spot.
Methods: Family history and clinical data were recorded. The genomic DNA was extracted from peripheral blood leukocytes. Microsatellite markers at loci considered to be associated with autosomal dominant cataracts were selected and genotyped for two-point linkage analysis. Direct sequencing was performed to identify the disease-causing mutation. Haplotype analysis was constructed to compare the affected haplotype in this family and in another Chinese family previously reported by us.
Results: Clinical features of cataract in this family were asymmetric in two eyes of some affected subjects. Evidence of linkage was obtained with marker D21S1411 (logarithm of odds [LOD] score [Z] = 2.42, recombination fraction [θ] = 0.0). Sequencing of the candidate CRYAA gene revealed a single base alteration c.347 G > A in exon 3, which resulted in the substitution of highly conserved arginine by histidine at codon 116 (p.R116H). This mutation co-segregated with all affected individuals and was not observed in unaffected family members or 100 normal unrelated individuals. The comparative haplotype analysis showed that the affected haplotypes in the two families were different.
Conclusions: This study identified a novel cataract-microcornea phenotype caused by the recurrent mutation p.R116H in CRYAA, and suggested that this mutation site is not likely the consequence of a founder effect, but probably a result of a mutational hot spot.