Benign Flecked Retina Disorder via the PLA2G5 Gene

Flecked retinal disorder is characterized by a distinctive retinal appearance with yellow-white, irregular fleck-like lesions with great variability in size, extending to the far periphery of the retina, but sparing the foveal region without vascular or optic nerve abnormalities. This condition is seen in a large variety of diseases. Some are limited to the eyes such as fundus albipunctatus, fundus flavimaculatus, familial drusen and fleck retina of Kandori, retinitis punctata albescens or Bietti's crystalline dystrophy, and neuro-ophthalmologic syndromes such as Kjellin's syndrome. These disorders differ in severity (De Laey. 1993. PubMed ID: 7952338). It is important to distinguish these types of flecks from each other for accurate diagnosis. Sabel Aish and Dajani summarized the different types of flecked retinal disorders (Sabel Aish and Dajani. 1980. PubMed ID: 7426586).

PLA2G5-associated benign fleck retina is characterized as widespread discrete yellow-white fleck lesions on the fundus extending to the far periphery, but sparing the macular region with normal visual acuity and normal electroretinogram (Isaacs et al. 1996. PubMed ID: 8703867).

Flecked retinal disorder (FRD) is heterogeneous as FRD is present in several retinal disorders with autosomal dominant, autosomal recessive, and x-linked inheritance. Pathogenic variants in ABCA4, CHM, EFEMP1, ELOVL4, LRAT, PLA2G5, PROM1, PRPH2, RDH5, RHO, RLBP1, RS1, and VPS13B have been shown to cause retinal flecks (Sergouniotis et al. 2011. PubMed ID: 22137173; Hayashi et al. 2006. PubMed ID: 16637847; Sparrow et al. 2015. PubMed ID: 26230768; Renner et al. 2009. PubMed ID: 19597113; Michaelides et al. 2003. PubMed ID: 12960208; Hipp et al. 2015. PubMed ID: 25429852; Littink et al. 2012. PubMed ID: 22559933; Souied et al. 1996. PubMed ID: 8554077; Yang et al. 2008. PubMed ID: 18654668; Taban et al. 2007. PubMed ID: 17383910).

Bi-allelic pathogenic variants in PLA2G5 cause benign fleck retina (Sergouniotis et al. 2011. PubMed ID: 22137173). PLA2G5 encodes group V phospholipase A2 (PLA₂), which is highly expressed in the eye and heart (Sergouniotis et al. 2011. PubMed ID: 22137173). PLA₂ is reported to be involved in phospholipid digestion and metabolism, host defense, and signal transduction (Dennis. 1994. PubMed ID: 8175726). To date, ~5 causative variants (missense, nonsense and a small frameshift deletion) have been documented causative (Human Gene Mutation Database).

Due to genetic heterogeneity and phenotypic overlap, the clinical sensitivity is unclear. So far, large deletions/duplications have not been documented in this gene (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the PLA2G5 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).