Identification of a novel SDCCAG8 gene variant in a family with retinitis pigmentosa and kidney failure

Abstract

Purpose : To describe the clinical phenotype and molecular analysis of a proband with autosomal recessive retinitis pigmentosa and kidney failure.

Methods : The clinical phenotype was characterized in a proband from a consanguineous family with four of nine siblings affected by retinal dystrophy and kidney failure. Visual function was assessed with visual acuity, semi-automated kinetic visual field, full field electroretinogram (ERG), fundus photography and ocular coherence tomography (OCT). Whole-genome sequencing (WGS) was performed on the proband using the Illumina protocols and HiSeqX10. The reads were aligned to human genome hg19 with decoy sequences using BWA-MEM with default parameters. Variant calling was performed using GATK following the best-practice pipeline guidance. The called variants were annotated based on frequency, ExAC, SnpEff, PolyPhen2, and CADD score. Mutational analysis of the mother and proband was performed by Sanger sequencing.

Results : The male proband experienced nyctalopia in the third decade and was diagnosed with retinitis pigmentosa in the fifth decade. The semi-automated kinetic visual field showed severe constriction with an inferior preserved visual island and the ERG was consistent with advanced retinal dystrophy in each eye. OCT exhibited outer retinal atrophy with foveal sparing in both eyes. Three other siblings experienced similar retinal dystrophy. All four affected family members had kidney failure. The WGS revealed a rare novel homozygous nonsense variant c.481C>T, p.Gln161* in the Serologically Defined Colon Cancer Antigen 8 (SDCCAG8 - NM_006642.3) gene and segregation analysis was confirmed with a maternal sample. TheSDCCAG8 gene is associated with nephronophtisis-related ciliopathies (OMIM #613524)

Conclusions : WGS analysis identified a novel homozygous nonsense variant p.Gln161* in the SDCCAG8 gene in a male proband affected by retinal-renal ciliopathy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.