Identification of a founder mutation in the PRPH2 gene in an isolated Pacific Island population

To characterize the phenotypic heterogeneity associated with a probable founder variant in the PRPH2 gene, in a Cook Island cohort presenting with variable retinal phenotypes.

Individuals carrying the same novel heterozygous PRPH2 variant were identified. Clinical evaluation included best-corrected visual acuity, fundus photography and autofluorescence, optical coherence tomography, electrophysiology, and visual field testing.

Five individuals (3 females, 2 males) were identified. Phenotypic manifestations included rod-cone dystrophy (n = 2), adult-onset vitelliform dystrophy, pattern dystrophy, and advanced global retinal atrophy (1 case each). Intrafamilial variability was observed in one pedigree. All affected individuals originated from the Cook Islands, suggesting a shared ancestral variant.

PRPH2-associated inherited retinopathy demonstrated marked phenotypic variability in this cohort. Recognition of a founder genetic variant within a geographically isolated population highlights the importance of targeted molecular testing and may inform the development of tailored gene-based 20 therapeutic strategies.