PLA2G5 and Stargardt Disease

Recent multi‐patient studies have identified novel PLA2G5 variants in patients diagnosed with Stargardt disease (MONDO_0019353). Although PLA2G5 is best known for its role in benign fleck retina, the detection of rare variants in this gene within large ar macular dystrophy cohorts suggests a possible, yet unconfirmed, extension of its phenotypic spectrum. In the context of Stargardt disease, the inheritance appears to be autosomal recessive and the genetic data are derived from studies that included limited numbers of probands without robust familial segregation data (PMID:35119454).

Genetic evidence is primarily supported by the recurrent missense mutation c.133G>T (p.Gly45Cys), initially reported in a consanguineous family with benign fleck retina (PMID:22137173). Functional assessments in ocular tissues have demonstrated PLA2G5 expression, yet these studies, while informative about retinal protein distribution, do not directly clarify the pathogenic mechanism leading to Stargardt disease (PMID:22467583). In summary, although current data hint at a potential association of PLA2G5 with Stargardt disease, further segregation and functional analyses are necessary to establish its clinical utility for diagnostic and therapeutic purposes.

References

• American Journal of Human Genetics • 2011 • Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign fleck retina PMID:22137173
• Investigative Ophthalmology & Visual Science • 2012 • Isoforms of secretory group two phospholipase A in mouse ocular surface epithelia and lacrimal glands PMID:22467583
• Multi‑patient study on macular dystrophies • 202X • Genetic landscape of ar/s macular dystrophies revealing novel phenotypic associations PMID:35119454

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