Characterization of PROM1 p.Arg373Cys Variant in a Cohort of Chinese Patients: Macular Dystrophy Plus Peripheral Bone-Spicule Degeneration

Purpose: The PROM1 p.Arg373Cys variant has been reported to cause dominant Stargardt disease, cone–rod dystrophy, and occasionally retinitis pigmentosa. This study aimed to evaluate the common phenotype associated with this variant in Chinese patients. Methods: Variants in PROM1 were collected from in-house exome data. Potential pathogenic variants were selected, verified, and then confirmed by Sanger sequencing and co-segregation analysis. Ocular phenotypes were reviewed and further clarified by ophthalmologic examinations. Results: The heterozygous c.1117C>T (p.Arg373Cys) variant was identified in four unrelated families, and biallelic variants were detected in three families. Of the 10 patients from four families with the p.Arg373Cys variant, six patients from three families who underwent full fundus examination demonstrated various degrees of macular dystrophy, as well as typical bone-spicule pigment deposits in the peripheral retina. The remaining four patients did not undergo a full dilated fundus examination. A relatively preserved zone was observed between the macular and peripheral lesions. Electroretinography results showed cone and rod involvement in three patients. Conclusions: Unlike Stargardt disease alone, which was considered to be the main phenotype of the p.Arg373Cys variant, all patients with full-field fundus examination in our study presented with macular dystrophy plus peripheral retinopathy resembling retinitis pigmentosa. Different phenotypes associated with the p.Arg373Cys variant may actually reflect different stages of the same disease: a predominant central cone phenotype at an early stage and peripheral rod involvement as degeneration progresses. Evaluation of the full fundus, especially the peripheral region in additional patients, is expected to confirm our findings.