Objective: To identify the genetic defect for the autosomal dominant coralliform cataract affecting a four-generation Chinese family.
Methods: Genomic DNA from the family members was typed for whole genomic linkage analysis. Two-point LOD scores were calculated using the LINKAGE program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing.
Results: Thirteen of the 38 individuals had congenital cataracts. The maximum two point LOD score, 3.5 at theta=0.1 was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin gene cluster identified a C --> A mutation in exon 2 of gamma-D crystallin gene (CRYGD) associated with cataracts in this family. This mutation resulted in a substitution of threonine for proline at amino acid 23 (P23T) of the protein.
Conclusion: The results suggest that the coralliform cataract phenotype is due to a mutated gamma-D gene, and the sequence change is identical with that recently reported to be related with lamellar cataract, a distinct clinical entity, thus providing evidence that the same genetic defect may be associated with different opacity location. The pathogenesis needs further investigation.