PRPH2 – Retinitis Punctata Albescens

PRPH2 encodes a photoreceptor-specific glycoprotein essential for rod and cone outer segment morphogenesis. In a 39-year-old female with nyctalopia (HP:0000662) and blurred vision (HP:0000622), a heterozygous splice-site variant, c.828+2T>C, was detected and co-segregated with the white punctate RPA phenotype in three additional relatives (mother, son, daughter), supporting autosomal dominant inheritance and involvement in four affected individuals in one family ([PMID:35042295]). The clustering of affected first-degree relatives with a single PRPH2 variant provides limited but compelling genetic evidence for disease causality in retinitis punctata albescens ([PMID:35042295]).

Functional rescue studies in the transgenic rds mouse model demonstrate that expression of wild-type Prph2 under an opsin promoter fully restores retinal morphology in high-expressing lines, definitively linking Prph2 insufficiency to photoreceptor dysplasia and degeneration ([PMID:1385966]). These in vivo findings delineate a loss-of-function mechanism for PRPH2 variants and reinforce the value of PRPH2 genetic testing in patients presenting with punctate retinal lesions. Key take-home: PRPH2 splice-site mutations should be considered in autosomal dominant retinitis punctata albescens, guiding diagnostic and therapeutic strategies.

References

• European journal of ophthalmology • 2022 • A PRPH2 gene variant detected in retinitis punctata albescens with congenital hypertrophy of the retinal pigment epithelium. PMID:35042295
• Neuron • 1992 • Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice. PMID:1385966

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