A Novel HSF4 Gene Mutation Causes Autosomal-Dominant Cataracts in a Chinese Family
PURPOSE The aim of this study was to map the disease locus of autosomal dominant cataracts (ADC) in a Chinese family. METHODS A four-generation family with multiple individuals affected by ADC was investigated. Genomic DNA was collected from 22 family members. A gene-scan at known candidate ADC loci was performed. To achieve fine-mapping we genotyped fourteen STR markers at the critical region of 19q. The two-point logarithm of odds (LOD) score was calculated using Linkage Software Package Version 5.1 for linkage analysis. The haplotype was constructed using Cyrillic software. RESULTS Ten members of this Chinese family were affected by nuclear cataracts. Initially, linkage analysis revealed a significant LOD score of 3.82 at the STR marker D19S418. Subsequently, after refine-marker analysis, a maximum LOD score (Z(max)=4.25) was obtained at the D19S877 (θ=0). Haplotype analysis also confirmed the locus and further narrowed it down to a critical interval from the marker D19S924 to the 19qter. CONCLUSIONS We have successfully mapped an ADC locus to 19q13-qter. Previous studies have identified three cataract loci on 19q; however, we found no overlap between the locus of this study and any of the previously identified loci. We therefore suggest that the 19q13-qter locus in this family is a new locus for ADC.