Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family.

Purpose: To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. . A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function.

Results: The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.

Conclusions: We report a novel mutation, p.C505S, and a known mutation, p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of p.C505S with iris coloboma has been demonstrated, although p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract. c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.