PRPH2 – Leber congenital amaurosis

PRPH2 pathogenic variants have been rarely reported in patients with Leber congenital amaurosis (LCA), primarily under an autosomal recessive model. A single consanguineous family was described in which a known nonsense variant, c.715C>T (p.Gln239Ter), segregated with early onset retinal dystrophy presenting as LCA–like disease in a homozygous proband. Heterozygous family members exhibited milder macular pattern dystrophy and fundus flavimaculatus. No additional LCA‐affected relatives were identified, supporting an AR loss-of-function mechanism (PMID:31618092).

Functional assays in the rds (Prph2) mouse model demonstrate that transgenic expression of wild-type PRPH2 fully rescues outer segment development and photoreceptor integrity in homozygous mutants, confirming that PRPH2 deficiency alone is sufficient to produce retinal degeneration mirroring human disease (PMID:1385966). Together, limited human segregation data and concordant animal rescue studies support a Limited clinical validity for PRPH2 in LCA. Key Take-home: Biallelic PRPH2 loss-of-function variants can underlie an AR LCA-like phenotype, guiding molecular diagnosis and potential gene-replacement strategies.

References

• Ophthalmic genetics • 2019 • PRPH2 mutation as the cause of various clinical manifestations in a family affected with inherited retinal dystrophy. PMID:31618092
• Neuron • 1992 • Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice. PMID:1385966

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