Retinitis Pigmentosa 7 via the ROM1 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). Causative variants in ROM1 cause recessive photoreceptor degeneration (Clarke et al 2000). Interestingly, digenic inheritance (ROM1 and PRPH2 variants) has been reported in three families and no heterozygous carriers of either pathogenic variant alone had RP. Only double heterozygotes had retinitis pigmentosa (Kajiwara et al. 1994). So far, about 10 pathogenic variants (missense, small deletions and duplications) have been reported in ROM1-associated RP (The Human Gene Mutation Database). Pathogenic variants in ROM1 also been reported in AD RP (Yanagihashi et al. 2003).

ROM1 encoded protein is localized to the outer segments of rod photoreceptors. Animal studies suggest that ROM1 is required for the regulation of disc morphogenesis and the viability of mammalian rod photoreceptors.

Sensitivity data are limited. It has been reported that ROM1 pathogenic variants occur in 1% or less of patients with AD RP or simplex RP (Bascom et al. 1992).

No documented gross deletions or duplications have been reported to date in ROM1 (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the ROM1 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).