PRPH2 – Multifocal Pattern Dystrophy Simulating Fundus Flavimaculatus

In a cohort of eight families (24 patients) with PRPH2 mutations, one patient carrying the heterozygous c.458AGA (p.Lys154del) variant presented with multifocal pattern dystrophy simulating fundus flavimaculatus (PDsFF) without evidence of segregation in relatives ([PMID:32660024]). Additional screening in macular dystrophy cohorts identified PRPH2 variants in pattern dystrophy cases but did not specifically confirm PDsFF, underscoring limited case‐level support for this specific gene–disease pairing.

PRPH2 encodes peripherin-2, a tetraspanin protein essential for photoreceptor outer segment (OS) morphogenesis. Transgenic rescue of the rds phenotype in mice via opsin-driven expression of wild-type PRPH2 restores normal OS architecture and function, providing mechanistic evidence that PRPH2 defects can underlie human retinal dystrophies ([PMID:1385966]).

Key Take-home: While PRPH2 variants, such as c.458AGA (p.Lys154del), can underlie PDsFF, the association remains limited by scarce familial segregation; PRPH2 should nonetheless be included in genetic testing panels for multifocal pattern dystrophies.

References

• Genes • 2020 • PRPH2-Related Retinal Diseases: Broadening the Clinical Spectrum and Describing a New Mutation PMID:32660024
• Neuron • 1992 • Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice. PMID:1385966

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