A missense mutation in the γD-crystallin gene GRYGDassociated with autosomal dominant congenital cataract in a Chinesefamily

[摘要] Purpose: To identify the genetic defect in autosomal dominantcongenital cataracts in a six generation Chinese family.Methods: Clinical and ophthalmological examinations were performedon the affected and unaffected family members. All the members weregenotyped with microsatellite markers at loci which were considered tobe associated with cataracts. A two-point LOD score was calculated usingthe Linkage package after genotyping. A mutation was detected by directsequencing using gene specific primers.Results: Clinical heterogeneity was observed within this family,three affected individuals showed nuclear cataract and others hadcoralliform cataracts. Significant evidence of linkage was obtained atmarkers D2S325 (LOD score [Z]=3.10, recombination fraction [θ]=0.0)and D2S1782 (Z=5.97, θ=0.0), respectively. Haplotype analysisindicated that the cataract gene was close to those two markers.Sequencing of the γD-crystallin gene (CRYGD) revealed a C>Ttransition in exon 2, that causes a conservative substitution of Arg toCys at codon 14 (R14C). This mutation co-segregated with all affectedindividuals and was not observed in unaffected or 100 normal unrelatedindividuals. Bioinformatic analyses also showed that a highly conservedregion was located at Arg14.Conclusions: This study is the first reported case with phenotype ofcoralliform/nuclear cataract that associated with the mutation ofArg14Cys (R14C) CRYGD.

[学科分类] 生物化学/生物物理