Study Of Pathogenic Genes In Three Families With Congenital Cataract

PurposeCongenital cataract is the leading cause of visual impairment and blindness during infancy and early childhood.The prevalence of congenital cataract was estimated to be 1–6 cases per 10,000 live births worldwide.The disease can occur as an isolated defect or accompanied by other ocular developmental abnormalities or as part of multisystem abnormalities.About 8%-25% of congenital cataract is related to heredity and autosomal dominant inheritance is the most common mode of inheritance.To date,over 40 genes have been identified for congenital cataract.Our study is to analyze molecular genetics in three Chinese families with congenital cataract and to describe the associated phenotypes by Next-generation Sequencing.MethodsWe investigated three congenital cataract families from the ophthalmology clinic of Zhengzhou University.All participants were questioned for family history and carried out detailed ophthalmological examinations including visual acuity testing,slit lamp microscopy and direct and fundus examination.DNA was extracted from peripheral blood and sequenced by Next-generation.The mutations were verified by Sanger sequencing and predicted the pathogenicity of proteins with bioinformatics software such as Polyphen-2、SIFT、PROVEAN and Mutation taster.ResultsThree gene mutations were found in three congenital cataract families,including missense mutation c.199G>T（p.Asp67Tyr）and c.176C>G（p.Pro59Arg）in GJA8,deletion mutation c.344₃52delACCGCCGCT（p.115₁18de lHRRYinsH）in CRYAA.The mutations occur in other patients in the family,but not in normal relatives and the bioinformatics software all indicated the pathogenicity change.ConclusionsOur findings provide three pathogenic mutations in three congenital cataract families.Cataract types include total cataract,spotted lens opacity and nuclear opacity.The findings widened the mutation spectrum and to deepen the understanding of the pathogenesis of congenital cataract.At the same time,it also accumulates the foundation for the future study of prenatal diagnosis and gene therapy of congenital cataract.