Novel mutation of in autosomal dominant congenital cataracts.

BACKGROUND

Congenital cataracts is the most common cause of childhood visual impairment and blindness worldwide. It is reported that about one quarter of congenital cataracts caused by genetic defects. Various gene mutations have been identified in hereditary cataracts so far. The purpose of the present study was to investigate the relationship between gap junction protein alpha 8 () gene mutation and congenital cataract.

METHODS

A pedigree with autosomal dominant congenital cataract was investigated and the peripheral venous blood was extracted from 18 family members. After the high-throughput targeted capture and whole exome sequencing for the proband, bioinformatics analysis was performed. By combining the proband clinical symptoms, candidate variations were eliminated which were significantly not consistent with the clinical phenotype. And disease-causing variant was identified.

RESULTS

Gene sequencing revealed the heterozygous missense mutation in exon 2 of the gene (c.178G>A), which co-segregated with the disease phenotype in the family and resulted in the substitution of glycine to serine at position 178 (p.G60S). This missense mutation was located in the hotspot mutation region, and might be harmful.

CONCLUSIONS

This study reports a novel disease-causing sequence variant in the gap junctional protein encoding genes causing autosomal dominant congenital cataract in the Chinese population, caused by the missense mutation of (c.178G>A). Our data expand the spectrum of variants and associated phenotypes, facilitate clinical diagnosis and support the presence of relationship between genetic basis and human disease.