Recurrent P23T change in CRYGD gene in two Chinese families with congenital coralliform cataracts / 中华实验眼科杂志

ABSTRACT

Background Clinical and genetic heterogeneity of congenital cataract is well substantiated.Researchers often identify disease loci by linkage analysis and screen candidate gene by direct sequencing.Objective This study was to localize and identify the disease-causing genes for two Chinese families with congenital coralliform cataracts.Methods Two Chinese families(CC1 and CC2) with autosomal dominant inheritance congenital coralliform cataracts were ascertained and patients in the families underwent ophthalmological examination.Periphery blood samples were collected and DNA was extracted from 17 subjects including 11 cataract patients and 4 phenotype normal and 2 spouses.A linkage scan of genomic regions containing 25 known candidate genes was performed using 50 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members and LOD scores were calculated.Candidate genes were sequenced and mutations were analyzed.Three single nucleotyde polymorphisms(SNP)(rs2305429,rs2305430,rs2242074) were sequenced and genotyped for the detect of the possibility of a common origin between CC1 and CC2.This study complied with the Declaration of Helsinki and was approved by Ethic Committee of Tianjin Eye Hospital.The informed consent was obtained from subjects and their guardian before the protocol.Results A significant LOD score of 3.28(θ=0) in family CC1 and a maximum LOD score of 1.50(θ=0) in family CC2 were both produced at the microsatellite marker D2S325 linked with CRYGD gene.Sequencing of CRYGD gene showed a heterozygous single base pair change c.70C＞A in exon2,predicting to result in a P23T amino acid change.The haplotypes of two probands in their respective families was quite distinct.Conclusion These results indicate that c.C70A(p.P23T) mutation in CRYGD gene is the underlyingmolecular pathogenesis of the two families with congenital coralliform cataracts,and this mutation occurs independently in these two families rather than descending from a common ancestor.