Identification Of The Pathogenic Gene In A Congenital Cataract Family

Congenital cataract, also known as the infantile cataract, can be defined as any opacity or cloudiness of the crystalline lens. A congenital cataract usually occurs within the first year of life. Congenital cataract is an important cause of visual impairment in children. The prevalence of congenital cataract is approximately1-6out of every10,000live births and8.3%to25%of congenital cataract is hereditary. The inheritace patterns of autosomal dominant, autosomal recessive and X-linked recessive have been reporting successively. Previous studies demonstrated that congenital cataract is a genetically heterogeneous disorder. To date, an lot of genetic loci such as3q21、13q11-q12、22q11are linked to congenital cataract and more than39genes such as GJA3, HSF4, MIP and so on have been identified.Objective:The aim of the present study was to identify the underlying pathogenic gene of a family with congenital cataract.Method:In this study, we collected a four-generation cataract pedigree of Chinese. We got36blood samples containing20patients of this family. First, a whole-genome scan and multipoint linkage analysis was performed with24individuals include18patients in this pedigree. Next, we conducted the hapmap to get the candidate region. Then we make a bioinformatics analysis whitin this region to determine the candidate genes. At last, we conducted a mutation analysis in order to find the pathogenic gene.Results:Through a whole-genome scan and multipoint linkage analysis, we localized the critical interval to chromosome22q with a maximum LOD score of3.26at rsl40390、rs743409and rs2283792. Haplotype analyses localized the critical interval to a4.3Mb interval on chromosome22q11.21-12.1between markers rs2283792and rs761670. According to the mechanisms of eye development, we searched for possible candidate genes between rs2283792and rs761670by candidate approach. We considered CRYBB2and CRYBB3which coding for crystalline as the first group of candidate genes. All coding exons and the boundary introns of CRYBB2and CRYBB3were amplified by polymerase chain reaction (PCR) and a G→C transition at nucleotide position c.453was identified. This mutation was identified in all affected individuals but is not found neither in the unaffected members in this family nor in any of the300controls.Conclusion:The mutation c.453G>C in CRYBB2gene is very likely the pathogenic mutation for this congenital cataract family.