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

PURPOSE: To identify the disease locus for nuclear congenital cataract in a nonconsanguineous family with two affected members. METHODS: One family with two affected members with congenital cataract and 170 normal controls were examined. DNA from leukocytes and bucal swabs was isolated to analyze the CRYGA-D cluster genes and microsatellite markers D2S325, D2S2382, and D2S126, and to discard paternity through gene scan with several highly polymorphic markers. RESULTS: DNA sequencing analysis of the CRYGA-D cluster genes of the two affected members showed a novel heterozygous missense mutation c.320A>C within exon 3 of the CRYGD gene. This transversion mutation resulted in the substitution of glutamic acid 107 by an alanine (E107A). Analysis of the two unaffected members of the family and the normal parents showed a normal sequence of the CRYGA-D cluster genes. This mutation was not found in a group of 170 unrelated controls. We consider that it is unlikely that this abnormal allele represents a rare polymorphism. DNA analysis showed no evidence for non-paternity while genotyping indicated that the haplotype of the mother co-segregated with the disease. CONCLUSIONS: In this study we describe the mutation c.320A>C (E107A) in the CRYGD gene associated with nuclear congenital cataract. Haplotype analysis strongly suggests that the origin of the mutation was transmitted through the mother.