Localization Of The Disease-associated Gene Of A Congenital Cataract Family

Purpose:Congenital cataracts are a significant cause of visual damage in children,resulting in approximately 10%of childhood blindness worldwide,with a prevalence of 0.6 to 6.0 in 10 000 live births.So far,over 39 independent loci and genes have been reported to be associated with inherited cataracts.Our study is to identify the disease-causing mutation which is responsible for the presence of congenital cataract in a Chinese family.Methods:The study recruited a four-generation Chinese pedigree affected by autosomal dominant congenital cataract(ADCC).There are 12 individuals participated in the study,5 affected and 7 unaffected.Family history and the history of cataract extraction were recorded.Blood samples were collected from individuals for DNA extraction.Direct sequencing of all the exons and flanking intronic sequences of congenital cataract-associated genes was performed.Single-strand conformational polymorphism and bioinformatic analysis were conducted to further study the mutation.Results:Direct sequencing revealed a novel splice site mutation of c.30-2 A>G in the CRYBA3/A1 gene.The mutation co-segregated within all affected individuals in the family and was not found in unaffected members or 100 unrelated normal controls.These results were further confirmed by single-strand conformational polymorphism and bioinformatic analysis using the Human Splicing Finder and MaxEnt online software and Annovar computer software.Conclusions:The heterogeneous c.30-2 A>G mutation of the CRYBA3/A1 gene in a Chinese family is a novel mutation.This missense mutation co-segregated well with the presence of congenital cataract.The study broadens the genetic spectrum of ADCC,further supporting the important role of the CRYBA3/A1 gene in human lens development and cataract formation.