Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Purpose: As the leading cause of the impairment of vision of children, congenital cataract is considered as a hereditary disease, especially autosomal dominant congenital cataract (ADCC). The purpose of this study is to identify the genetic defect of six Chinese families with ADCC.Subjects and Methods: Six Chinese families with ADCC were recruited in the study. (103 members in total, 96 members alive, 27 patients in total) Genomic DNA samples extracting from probands’ peripheral blood cells were captured the mutations using a specific eye disease enrichment panel with next generation sequencing. After initial pathogenicity prediction, sites with specific pathogenicity were screened for further validation. Sanger sequencing was conducted in the other individuals in the families and other 100 normal controls. Mutations definitely related with ADCC will then be analyzed by bioinformatics analysis. The pathogenic effect of the amino acid changes and structural and functional changes of the proteins were finally analyzed by bioinformatics analysis.Results: Seven mutations in six candidate genes associated with ADCC of six families were detected (MYH9 c.4150Gu003eC, CRYBA4 c.169Tu003eC, RPGRRIP1 c.2669Gu003eA, WFS1 c.1235Tu003eC, CRYBA4 c.26Cu003eT, EPHA2 c.2663+1Gu003eA, and PAX6 c.11-2Au003eG). All the seven mutations were only detected on affected individuals in the families. Among them there are three novel mutations (MYH9 c.4150Gu003eC, CRYBA4 c.169Tu003eC, RPGRRIP1 c.2669Gu003eA) and four that have been reported (WFS1 c.1235Tu003eC, CRYBA4 c.26Cu003eT, EPHA2 c.2663+1Gu003eA, and PAX6 c.11-2Au003eG). RPGRIP1 (c.2669Gu003eA) mutation and CRYBA4 (c.26Cu003eT) mutation are predicted to be benign according to bioinformatics analysis while the other five mutations (EPHA2, PAX6, MYH9, CRYBA4 c.169Tu003eC, WFS1) are thought to be pathogenic.Conclusion: We report two novel heterozygous mutations (MYH9 c.4150Gu003eC and CRYBA4 c.169Tu003eC) in six Chinese families supporting their vital roles in causing ADCC.