Target region sequencing in sporadic congenital cataracts reveals a new genotype-phenotype relation for the GALK1 gene
Abstract
Purpose
The purpose of this study was to investigate the genetic effects underlying sporadic congenital cataracts (SCC).
Methods
We collected DNA samples from 74 SCC patients and 20 traumatic cataract (TC) patients in the same age group as normal controls and performed genomic sequencing of 61 cataract-related genes (including introns, exons and 10 bases from the 3′ and 5′ ends) by target region capture and next generation sequencing. We chose previously reported cataract-related genes and also included other lens disease-related genes, including microphthalmia (SOX2, PAX6, OTX2, RAX, FOXE3 and CRYBA4); aniridia (FOXC1, PITX2 and PITX3); Marfan syndrome (FBN1); ectopia lentis (ADAMTSL4 and ADAMTS17) and Alport syndrome (COL4A5).
Results
By filtering the SNPs that were previously deposited in the NCBI SNP database (dbSNP) or were associated with TC cases, we identified 72 novel variants in 40 genes from 49 patients. The mutation frequency of the GALK1 gene was much higher than the other tested genes, with mutations detected 10 times in 7 patients; followed by CRYBB3 and FBN1 the mutation of which were detected 4 times. Moreover, we observed a posterior polar-cataract phenotype in 86% (6 out of 7) of SCC patients with mutations in GALK1.
Conclusions
We conclude that genetic mutations could be important contributing factors to non-hereditary congenital cataract; for example, GALK1, the most frequently mutated gene in this group of patients, was related to the posterior polar subtype of cataract.
