Localization Of The Pathogenic Gene And Detection Of The Mutation Of A Congenital Cataract Family

Purpose:Congenital cataract is a common ocular disorder among infants and children, its prevalence is about1-15per10000live birth worldwide. About10-25%of congenital cataract is related to genetic change, with autosomal dominant inheritance as the most common pattern. Up to date, congenital cataract is one of the main causes of children visual impairment and blindness. With a complicated genetic causative mechanism itself, not only one gene is responsible for the pathogenesis. Review of the earlier researches in this field suggests that more than20causative genes has been found. Our study is to analyze a Chinese family with congenital cataract and to localize and detect the pathogenic gene of the family.Methods:Our research is to study a4generation family suffers from congenital cataract.8individuals was affected among32individuals that participated in this study. All members were questioned for the detailed family history and required a serial of ophthalmological examinations, including slit-lamp examination, visual acuity testing and fudus examination. Draw peripheral blood and extract genomic DNA samples of all family members and100unaffected people. The target fragment of candidate gene were amplified by polymerase chain reaction and the DNA sequence were bidirectional detected. Sequence were analyzed to determine the pathogenic gene in the family, and used the related software to predict whether the protein function was affected due to genetic change.Results:The affected pedigree showed a phenotype of lamellar cataract by slit-lamp examination. According to the genealogy, the family’s hereditary pattern was identified as autosomal dominant. The result of the gene sequencing illustrated a heterozygous c.34C>T change in the first exon region of the CRYAA gene, resulting in the replacement of the12th amino acid from arginine to cysteine (p.R12C). The same mutation was found in all8affected individuals, but in none of the unaffected family members nor the100healthy controls. The p.R12C mutation co-segregated with the affected individuals in the family. The amino acid substitution in this loci led to the increase of hydrophobicity in the local and near area, and the mutation was probably deleterious. Refer to the earlier researches, this mutation was involved in the occurrence of congenital cataract, and it was the pathogenic mutation in the study family.Conclusions:Our study revealed a heterozygous c.34C>T mutation of the CRYAA gene in a Chinese congenital cataract family. It was a missense mutation and it co-segregated with the congenital cataract. Combine with the earlier researches, our study supported the pathogenicity of the mutated CRYAA gene in this loci toward the congenital cataract.