PURPOSE To investigate the molecular genetic background in Chinese families with autosomal dominant nuclear cataract.
METHODS Members of thirty unrelated Chinese families with congenital nuclear cataracts and 100 unrelated individual adults without congenital cataracts were recruited for this study. All study subjects were given full ophthalmological examinations. The genomic DNA was extracted from peripheral blood leukocytes. We conducted two-point linkage analysis and sequencing of 18 cataract candidate genes to find the causative mutations.
RESULTS There were variations in the clinical phenotypes among families but all involved nuclear opacifications. Among the thirty families, six showed nuclear cataract and microcornea. Mutation analysis revealed seven causative mutations, five novel and two reported. Five families (16.7%) have affected crystalline genes, CRYAA-R116C, R116H, CRYBB2-V146M, I21N, CRYBB1- R233H. Two families (6.7%) had mutations in the GJA8 gene, I31T and S258F. These mutations co-segregated with all affected individuals in the respective families and were not observed in unaffected family members or the 100 controls.
CONCLUSIONS Mutations were identified in 7 out of the30families (23.3%). All these mutations involve in crystallins and connexins. The CRYBB2 mutation (V146M) was first identified in this study to be associated with congenital cataract and microcornea. Our results, with 67.7% of families not identified for mutations in reported genes, strongly indicates the genetic heterogeneity of congenital cataracts, although the crystalline genes appear to be more commonly associated with hereditary nuclear cataracts than other genes in the Chinese population. |
