PCARE-associated inherited retinal diseases: clinical and molecular insights from a Portuguese population

PCARE-associated inherited retinal diseases are rare disorders characterized by progressive vision loss due to photoreceptor degeneration. Although several variants have been identified in diverse populations, limited data are available from the Iberian Peninsula.

We conducted a retrospective case series of eight Portuguese patients from six unrelated families with confirmed PCARE mutations. Clinical data, multimodal imaging, and genetic analyses were reviewed.

The most common variant identified was c.3099delinsCCAGG p.(Val1034Glnfs *74), present in homozygosity in five patients from 4 families and in heterozygosity with a variant of uncertain significance in one patient, suggesting a potential regional founder effect. All patients exhibited symptoms beginning in the third to fifth decades, primarily decreased visual acuity, visual field constriction, photophobia, and nyctalopia. Fundoscopy findings included bone spicule, perifoveal retinal atrophy with foveal sparing, and arteriolar narrowing. Optical coherence tomography showed thinning of the outer retinal layers. Two patients also showed foveal involvement and severe visual loss. The clinical phenotype was consistent with both rod-cone and cone-rod dystrophy.

Our findings suggest that this variant may be enriched in the Portuguese population. Further studies are needed to confirm the founder effect hypothesis and to guide future therapeutic strategies targeting PCARE-associated retinal degeneration.