Genetic Mapping In Two Chinese Family With Autosomal Dominant Congenital Cataract

Background and objectiveCongenital cataract is a common blindness threatening disease among children. The epidemiological studies have shown that the prevalence ratio in our country was0.05%, and in European and American countries the prevalence was0.01～0.06%. Among them, about one-third of congenital cataract has transmissibility. Autosomal dominant congenital cataract is the most common pattern of hereditary cataract, it can continuous transmission in the family,not only make patients and families painful, but brings a large burden to the society.Until now,thirty-nine loci have been mapped in the hereditary congenital cataracts, and twenty-six genes have been cloned in these loci.But the the relationship between clinical phenotype and the genotypes had still not completely clear, therefore, we should find more related genes and mutations through the further study of congenital cataract to clarify the molecular genetics of congenital cataract mechanism,and establish genetic counseling and prenatal gene diagnosis technology. This study collected two autosomal dominant congenital cataract family in Henan province of China to find the pathologic mechanism of congenital cataract.Materials and MethodsTwo congenital cataract family in Henan province of China were collected in this study,family A is coralliform cataract family of five generation and family B is pulverulent nuclear cataract family of four generation,two of the patients in family B is cerulean and posterior polar cataract. We collected family materials to make family genealogy map,and gave them physical examination to exclude other ocular abnormalities and systematic diseases. After signed the informed consent, gathering family members peripheral blood5ml, genomic DNA was extracted from their blood using phenol-chloroform extraction method.21polymorphic microsatellite markers in candidate genes CRYAA, CRYAB, CRYBA1, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS, GJA3, GJA8, EPHA2, MIP, BFSP2, PITX3, PAX6, MAF, HSF4was selected for Polymerase Chain Reaction (PCR) amplification,6%denaturing polyacrylamide gel electrophoresis and silver staining to determine the genotypes and validated by sequencing.Two-point linkage analysis between the cataract phenotype and genetic markers were performed using the MLINK. Candidate genes exon gene sequencing were used to identify the mutation of the family. SWISS-MODEL and SWISS-PDBVIEWER are used to predicte the mutations in proteins.ResultsLinkage analysis provided evidence for linkage between the pathogenic gene of family A and microsatellite marker D1S218in chromatosome1q21-25, sequencing results show no obvious mutation of the candidate gene sequence GJA8exons in this region, and linkage analysis provided evidence for linkage between the pathogenic gene of family B and microsatellite marker D13S260in chromatosome13q11-13, sequencing results show exon377C missing(c.377delC) in the candidate gene sequence GJA3in this region.The prediction of the protein shows that the mutated protein loss the normal structure.ConclusionGJA8is not the pathogenic gene of the coralliform cataract family. c.377delC in the GJA3may be one of the pathogenic gene of pulverulent nuclear cataract.