Two affected siblings with nuclear cataract associated with anovel missense mutation in the CRYGD gene

[摘要] Purpose: To identify the disease locus for nuclear congenitalcataract in a nonconsanguineous family with two affected members.Methods: One family with two affected members with congenitalcataract and 170 normal controls were examined. DNA from leukocytes andbucal swabs was isolated to analyze the CRYGA-D cluster genes andmicrosatellite markers D2S325, D2S2382, and D2S126, and to discardpaternity through gene scan with several highly polymorphic markers.Results: DNA sequencing analysis of the CRYGA-D cluster genes ofthe two affected members showed a novel heterozygous missense mutationc.320A>C within exon 3 of the CRYGD gene. This transversionmutation resulted in the substitution of glutamic acid 107 by an alanine(E107A). Analysis of the two unaffected members of the family and thenormal parents showed a normal sequence of the CRYGA-D clustergenes. This mutation was not found in a group of 170 unrelated controls.We consider that it is unlikely that this abnormal allele represents arare polymorphism. DNA analysis showed no evidence for non-paternitywhile genotyping indicated that the haplotype of the motherco-segregated with the disease.Conclusions: In this study we describe the mutation c.320A>C(E107A) in the CRYGD gene associated with nuclear congenitalcataract. Haplotype analysis strongly suggests that the origin of themutation was transmitted through the mother.

[学科分类] 生物化学/生物物理