Congenital cataract is one of the important reasons for the blindness of children, and most congenital cataracts are genetic.At present, thirty-nine genes have been identified relating to autosomal dominant congenital cataract (ADCC).

This study was to identify and analyze the virulence gene of a Chinese family pedigree with ADCC by whole-exome sequencing.

A Chinese ADCC family was recruited in Affiliated First Hospital of Zhengzhou University from August to September in 2014.The family disease history and clinical data were recorded.The peripheral venous blood of 10 ml was collected in 14 patients with congenital cataract and 14 families with normal phenotype, and the peripheral blood samples were obtained from 100 healthy examined people as controls.The genomic DNA was extracted form all subjects using standard phenol chlorum method, and proband DNA was screened by whole-exome sequencing.Then mutation locus of the candidate gene was selected after compared with the information of database in the proband.The mutation locus of the candidate gene from 14 normal families and 100 healthy controls were amplified and sequenced by PCR technique based on the primer sequence of mutation locus of proband to verify the pathogenic gene of this ADCC family.This study protocol was approved by Ethic Committee of Affiliated First Hospital of Zhengzhou University and complied with Helsinki Declaration.Written informed consent was obtained from subjects or custodian before any medical examination.

The family had a total of 5 generations of 68 members, in which 20 subjects were found with congenital cataract.The inheritance mode consisted with autosomal dominant inheritance.Cortical cataract was found in both eyes in the patients.Whole-exome sequencing showed that the 143rd ribonucleotide A of exon 2 explicit factor of chromosome 13 GJA3 gene mutated into G (c.143A>G) in the proband, which resulted in the 48th amino acids changed from glutamate into glycine (p.E48G). PCR amplification product sequencing displayed that the same mutation of DNA appeared in all the patients of this family, while not the same mutation was seen in the candidate genes of normal phenotype families and 100 healthy controls. Conclusions GJA3 gene c. 143A>G is a virulence mutation site in this ADCC family, it is a supplement of the mutation spectrum of GJA3 gene.

Cataract/genetics; Connexins/genetics; Mutation, missense; Whole-exome sequencing; Amino Acid Sequence