Retinitis Pigmentosa via the CNGB1 Gene

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal disorders leading to blindness 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 22, 41 and 3 genes have been identified that are involved with AD, AR and XL forms, respectively (RetNet).

Pathogenic variants in CNGB1 gene are associated with autosomal recessive Retinitits pigmentosa (AR RP) (Bareil et al. 2001. PubMed ID: 11379879). CNGB1 encodes the beta-subunit of the rod cGMP-gated channel. Beta-subunits alone cannot form functional cyclic nucleotide-gated (CNG) channels. However, mice studies showed that in the absence of CNGB1, only trace amounts of the alpha- subunit CNGA1 were found on the rod outer segment and showed no rod-mediated responses. The mutant mice also showed a slow-progressing rod degeneration (Hüttl et al. 2005. PubMed ID: 15634774).

To date , over 40 CNGB1 pathogenic variants (missense, nonsense, splicing and a small frameshift deletions and duplications) have been documented causative for AR RP (Human Gene Mutation Database).

Two studies reported that variants in CNGB1 account for ~4% of autosomal recessive Retinitis Pigmentosa cases (Hull et al. 2017. PubMed ID: 28056120; Ge. 2015. PubMed ID: 26667666).

This test provides full coverage of all coding exons of the CNGB1 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).