Localization and screening of autosomal dominant coralliform cataract associated gene / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To identify the genetic defect for the autosomal dominant coralliform cataract affecting a four-generation Chinese family.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>