Purpose  To report and identify the genetic defect that causes novel variable cataracts and microcornea in a Chinese family.
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.
Results  All of the affected individuals had congenital cataract and microcornea. Clinical features of cataract were asymmetric in two eyes of some affected subjects. Significant evidence of linkage was obtained at marker D21S1890 (logarithm of odds [LOD] score [Z]=1.90, recombination fraction [θ]=0.0). Sequencing of the candidate αA-crystallin (CRYAA) gene revealed a G>A transition at nucleotide position c.347. This nucleotide change resulted in the substitution of highly conserved arginine by histidine at codon 116 (R116H). This mutation co-segregated with all affected individuals and was not observed in unaffected or 100 normal unrelated individuals.
Conclusions  This study identified a mutation (R116H) in CRYAA in a Chinese family with a novel congenital cataract-microcornea phenotype and confirmed the phenotypic heterogeneity of this mutation.