Autosomal Recessive Retinitis Pigmentosa (RP) Panel

Retinitis pigmentosa (RP) represents a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4000 (Booij 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 and syndromic RP is remarkably heterogeneous both clinically and genetically and exhibits autosomal dominant (AD, 15%-25% of the cases), autosomal recessive (AR, 5%-20% of the cases) or X-linked (XL, 5%-15% of the cases) inheritance (Fahim et al. 2013). Unknown, simplex cases (single occurrence in a family) account for 40%-50%of cases and rarely digenic inheritance has been reported (Fahim et al. 2013). To date, over 80 genes have been linked to RP (RetNet; Daiger et al. 2007; Daiger et al. 2013; Audo et al. 2012; Neveling et al. 2012; Fu et al. 2013; Zhao et al. 2015; http://www.omim.org/; Human Gene Mutation Database), but likely more RP genes remain to be discovered (Daiger et al. 2010; Daiger et al. 2013; Perez-Carro et al. 2016).

The most common genes involved in AR RP are USH2A (10-15%), ABCA4 (2-5%), PDE6A (2-5%), PDE6B (2-5%), RPE65 (2-5%), and CNGA1 (1-2%). BEST1, PCARE (C2ORF71), C8ORF37, CLRN1, CNGB1, DHDDS, FAM161A, IDH3B, IMPG2, LRAT, MAK, MERTK, NRL, PDE6G, PRCD, PROM1, RBP3, RGR, RHO, RLBP1, RP1, SAG, SPATA7, TTC8, CERKL, TULP1, ZNF513, and ARL6 each account for less than 1% of RP cases (Fahim et al. 2013).See individual gene test descriptions for more information on molecular biology of gene products.

It is now possible to detect disease-causing pathogenic variants in about 30% of patients with recessive RP (Daiger et al. 2010).

Genomic rearrangements in PRPF31 are now known to account for 2.5% of AD RP (Sullivan et al. 2006). Relatively common deletions and rearrangements are also found in ABCA4, which is causative for AR RP (Yatsenko et al. 2003). In addition, copy number variants have been reported in ABHD12, ARL6, BEST1, CEP290, CRB1, EYS, GUCY2D, IMPG2, MERTK, NR2E3, PDE6B, PRPF31, PRPH2, RDH12, RHO, RLBP1, RPE65, RPGRIP1, SAG, SPATA7, TULP1 and USH2A (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.8% coverage of all coding exons of the genes 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 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).