A Survey of DNA Variation of C2orf71 in Probands With Progressive Autosomal Recessive Retinal Dystrophy

Abstract

Purpose: : Mutation of C2orf71 was recently reported to be associated with retinitis pigmentosa (RP) in humans with knockdown of the gene causing defects in vision in zebrafish¹. The C2orf71 gene is located on 2p23.2, is conserved in euteleostomi but has no evident paralogues. In humans, it is a 2-exon gene, predicted to encode a 1288 amino acid protein which is expressed mainly in the retina. We sought to determine the prevalence of mutations in C2orf71 in cohorts of probands with recessive retinal degeneration and controls.

Methods: : 288 affected unrelated individuals were evaluated for DNA variants using high-resolution DNA melting analysis (LightScanner®, Idaho Tech, USA) and Sanger sequencing (ABI Prism 3100, Applied Biosystems Inc, USA). 96 of these are affected with recessive Leber’s Congenital Amaurosis (LCA)/ Early Onset Retinal Dystrophy and had been negative for mutations in known genes. The remaining 192 individuals are affected with autosomal recessive adult onset rod-cone or cone-rod dystrophy, in whom the molecular diagnosis was unknown. 151 European and 40 South Asian control DNAs were also screened in a similar fashion.

Results: : Many DNA sequence variants were detected. 16 novel single nucleotide polymorphisms (SNPs) were found in controls and affected individuals (12 missense, 4 synonymous). Importantly, so far, 10 novel sequence variants in 19 probands (6.6%) were detected in our cohort of patients but not in controls. These include 6 missense, 1 in frame 3-base pair deletion and 3 synonymous changes. Only 2 probands were compound heterozygotes, one with severe LCA and another with autosomal recessive RP.

Conclusions: : C2orf71

Keywords: retinal degenerations: hereditary • genetics • gene screening