Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population

Abstract

Purpose: This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC).

Methods: We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination.

Results: By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes.

Conclusions: From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC.

Figure 1

The mutation frequencies of the selected genes. A: The mutations in genes responsible for autosomal dominant or X-linked lens disease. B: The mutations in genes responsible for autosomal recessive lens disease. Black bar, total number of mutations; gray bar, number of mutations in the patients with bilateral cataract.

Figure 2

The NHS homozygous mutation identified in patient 59. The sequence chromatography and pedigree of patient 59 showed that the homozygous mutation of NHS was inherited from the patient’s mother.