Retinitis Pigmentosa 58 (RP58) via the ZNF513 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, 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 adRP, arRP, and XLRP, respectively (RetNet).

Pathogenic variants in ZNF513 cause arRP (Naz et al. 2010). ZNF513 encodes a putative transcription factor, which is expressed in the retina. Knockdown of ZNF513 in zebrafish resulted in reduced eye size, reduced retinal thickness, and reduced expression of rod and cone opsins. This in turn caused loss of photoreceptors. These studies suggested that ZNF513 plays a key role in the regulation of photoreceptor-specific genes in retinal development and photoreceptor maintenance (Li et al. 2010). Only a single missense variant in this gene has been reported to date (Human Gene Mutation Database).

Predicting clinical sensitivity for the ZNF513 gene is difficult due to the genetic heterogeneity of retinitis pigmentosa and the very few cases reported so far (Naz et al. 2010; Li et al. 2010). However, the paucity of cases suggests that pathogenic variants in ZNF513 are a relatively rare cause of Retinitis Pigmentosa.

This test provides full coverage of all coding exons of the ZNF513 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).