Exome sequencing identifies novel and recurrent mutations in GJA8 and CRYGD associated with inherited cataract.

ABSTRACT: BACKGROUND:Inherited cataract is a clinically important and genetically heterogeneous cause of visual impairment. Typically, it presents at an early age with or without other ocular/systemic signs and lacks clear phenotype-genotype correlation rendering both clinical classification and molecular diagnosis challenging. Here we have utilized trio-based whole exome sequencing to discover mutations in candidate genes underlying autosomal dominant cataract segregating in three nuclear families. RESULTS:In family A, we identified a recurrent heterozygous mutation in exon-2 of the gene encoding ?D-crystallin (CRYGD; c.70C?>?A, p.Pro24Thr) that co-segregated with 'coralliform' lens opacities. Families B and C were found to harbor different novel variants in exon-2 of the gene coding for gap-junction protein ?8 (GJA8; c.20T?>?C, p.Leu7Pro and c.293A?>?C, p.His98Pro). Each novel variant co-segregated with disease and was predicted in silico to have damaging effects on protein function. CONCLUSIONS:Exome sequencing facilitates concurrent mutation-profiling of the burgeoning list of candidate genes for inherited cataract, and the results can provide enhanced clinical diagnosis and genetic counseling for affected families.

SUBMITTER: Mackay DS 

PROVIDER: S-EPMC4240822 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature