Autosomal Dominant Retinitis Pigmentosa via the SNRNP200 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 AD RP, AR RP, and XL RP, respectively (RetNet). Pathogenic variants in SNRNP200 have been documented to cause AD RP (Zhao et al. 2006; Zhao et al. 2009). In vitro studies suggest that the SNRNP200-encoded protein [hBrr2, a U4/U6-U5 small nuclear ribonucleoprotein (snRNP) complex of the spliceosome] is involved in the unwinding of U4/U6 snRNAs during spliceosome activation and for disassembly of the spliceosome (Zhao et al. 2009). So far, over 15 pathogenic variants (missense and splicing) have been reported in SNRNP200-associated RP (The Human Gene Mutation Database).

Due to phenotypic and genotypic heterogeneity, estimation of clinical sensitivity is difficult. Mutation screening in a four-generation family identified a causative SNRNP200 variant in all affected family members (14) and that variant was absent in the unaffected family members and 100 normal control subjects (Liu et al. 2012).

This test provides full coverage of all coding exons of the SNRNP200 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).