Autosomal Recessive Retinitis Pigmentosa via the EYS Gene

Retinitis pigmentosa (RP) or rod cone dystrophies (RCDs) represent a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4,000 (Booij et al. 2005). RP is clinically characterized by retinal pigment deposits visible on fundus examination, nyctalopia ("night blindness"), followed by progressive degeneration of the photoreceptors, which eventually leads to blindness (van Soest et al. 1999).

Nonsyndromic RP is remarkably heterogeneous both clinically and genetically and exhibits autosomal dominant (AD), autosomal recessive (AR) or X-linked (XL) inheritance. To date, over 50 loci have been linked to nonsyndromic RP and 18, 27 and 2 genes have been identified that are involved with AD RP, AR RP, and XL RP, respectively (RetNet). Pathogenic variants in EYS have been documented causative for AR RP (Ruiz et al. 1998). EYS (eyes shut) encodes a Drosophila spacemaker (SPAM) protein that is localized to the photoreceptor layer. SPAM helps in maintaining the integrity of the photoreceptor cells in human retina (Abd El-Aziz et al. 2008). Nearly 200 pathogenic variants (missense, nonsense, splicing, small deletions and duplications, gross deletions and duplications) have been reported in EYS-associated retinal disorders (The Human Gene Mutation Database).

Mutation screening in 100 Japanese autosomal recessive retinitis pigmentosa (AR RP) patients identified EYS causative variants in 18% (Hosono et al. 2012). A Homozygosity mapping study reported that 10%-20% of Spanish families affected by typical AR RP could have linkage to the EYS locus (Ruiz A et al. 1998).

This test provides full coverage of all coding exons of the EYS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.