Autosomal Recessive Retinitis Pigmentosa 77 (RP77) via the REEP6 Gene

Retinitis pigmentosa (RP) represents a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4,000 (Booij et al. 2005. PubMed ID: 16272259). 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. PubMed ID: 10025514).

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 associated with AD, AR, and XL RP, respectively (RetNet).

Pathogenic variants in REEP6 have been documented causative for autosomal recessive Retinitis pigmentosa (Arno et al. 2016. PubMed ID: 27889058). REEP6 encodes a putative endoplasmic reticulum (ER) shaping factor called Receptor Expression Enhancer Protein 6, which is highly expressed in rod photoreceptor cells of developing and mature retina (Arno et al. 2016. PubMed ID: 27889058; Hao et al. 2014. PubMed ID: 24691551). The REEP6 protein is a key functional target of the Maf-family leucine zipper transcription factor NRL in rod photoreceptors and probably plays a role in trafficking of membrane proteins such as GPCRs (G-protein coupled receptors) to distinct cellular compartments (Hao et al. 2014. PubMed ID: 24691551). To date, ~ 5 pathogenic variants (missense and small frameshift deletion/duplications) in REEP6 have been connected to RP (Human Gene Mutation Database).

Predicting clinical sensitivity for the REEP6 gene is challenging due to genetic heterogeneity of retinal disorders and also due to the limited number of REEP6-associated retinitis pigmentosa cases.

This test provides full coverage of all coding exons of the REEP6 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).