Purpose: The molecular characterization of an Indian family having 10 members in four generations affected with a unique fan-shaped cataract-microcornea syndrome.
Methods: Detailed family history and clinical data were recorded. A genome-wide screening by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bi-directional sequencing of amplified products.
Results: The cataract-microcornea locus in this family was mapped to a 23.5 cM region on chromosome 21q22.3. Direct sequencing of the candidate gene CRYAA revealed a heterozygous C>T transition resulting in the substitution of the highly conserved arginine at position 116 by cysteine (R116C).
Conclusions: This study provides the report of mapping a locus for syndromal cataract (cataract-microcornea syndrome) on 21q22.3. The mutation observed in CRYAA in the present family highlights the phenotypic heterogeneity of the disorder in relation to the genotype, as an identical mutation has previously been reported in an American family with a different type of cataract. The "fan-shaped cataract" observed in the present family has not been reported before.