Flecked Retina Disorder Panel

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). 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).

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; Hayashi et al. 2006; Sparrow et al. 2015; Renner et al. 2009; Michaelides et al. 2003; Hipp et al. 2015; Littink et al. 2012; Souied et al. 1996; Yang et al. 2008; Taban et al. 2007). Missense, splicing, nonsense, small and gross deletions/duplications have been reported in these genes (Human Gene Mutation Database).

See individual gene test descriptions for more information on molecular biology of gene products.

Due to the genetic heterogeneity and phenotypic overlap, determining the clinical sensitivity is difficult. Shroyer et al. (2001) screened 22 families with both Stargardt disease (STGD) and Age-related Macular Degeneration and detected causative ABCA4 pathogenic variants in 37/46 (80%) (Shroyer et al. 2001).

So far, large deletions/duplications have been reported in ABCA4, CHM, PROM1, PRPH2, RHO, RLBP1, RS1, and VPS13B (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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).