Autosomal Recessive Retinitis Pigmentosa 36 (RP36) via the PRCD Gene

Retinitis pigmentosa (RP) or rod cone dystrophies (RCDs) represent a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4000 (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 adRP, arRP, and XLRP, respectively (RetNet).

Bi-allelic pathogenic variants in PRCD (Progressive rod-cone degeneration) are involved in late-onset retinitis pigmentosa (RP36). Bull's eye maculopathy seems to be a hallmark of PRCD-associated RP (Pach et al. 2013; Zangerl et al. 2006). PRCD encoded protein possibly plays a role in photoreceptor structure or metabolism unique to vertebrate visual cells. Immunocytochemical subcellular localization experiments have shown that the mutant form of the protein exhibits a distinct pattern of localization into spherical profiles within the cytoplasm. This altered localization might impair the interactions with other proteins in affected patients (Zangerl et al. 2006). So far, about 5 pathogenic variants (missense and nonsense) have been associated with arRP36 (Human Gene Mutation Database).

PRCD pathogenic variants account for nearly 1% of late-onset Retinitis Pigmentosa (RP) cases (Beheshtian et al. 2015). A study that screened 24 RP patients from an Israeli Muslim Arab village identified a homozygous nonsense PRCD variant (c.64C>T, p.R22*), which suggests a founder effect (Nevet et al. 2010). The same variant was also found in a Persian family with the late-onset non-syndromic arRP (Beheshtian et al. 2015).

This test provides full coverage of all coding exons of the PRCD gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).