A novel mutation in GJA8 associated with autosomal dominantcongenital cataract in a family of Indian origin

[摘要] Purpose: To identify the genetic defect in an autosomal dominantcongenital cataract family, having 15 members in three generations,affected with bilateral cataract that gave the appearance of "full moon"with Y-sutural opacities.Methods: A detailed family history and clinical data were recorded.A genome-wide scan by two point linkage analysis using nearly 400microsatellite markers in combination with multipoint lod score andhaplotype analysis was carried out. Mutation screening was performed inthe candidate gene by bidirectional sequencing of amplified products.Results: A maximum two point lod score of 5.45 at θ=0.00 wasobtained with marker D1S534. Haplotype analysis placed the cataractlocus to a 14.1 cM region between D1S221 and D1S498, in close proximityto the gene for the gap junction channel protein connexin 50 (GJA8)at 1q21. Mutation screening in GJA8 identified a novel G>Ctransversion at nucleotide position c.235. This nucleotide changeresulted in the substitution of highly conserved valine by leucine atcodon 79 (V79L). This nucleotide substitution was neither seen in anyunaffected member of the family nor in 180 unrelated control subjects(360 chromosomes) from same ethnic background tested by sequenceanalysis of GJA8.Conclusions: The present study describes the mapping of a locus forcongenital cataract that appeared like "full moon" with Y-suturalopacities at 1q21 and identifies a previously unreported mutation inGJA8. These findings thus expand the mutation spectrum of GJA8.

[学科分类] 生物化学/生物物理