Identification of a Pathogenic Variant in the Retinitis Pigmentosa1 Gene in a Sudanese Family with Retinitis Pigmentosa: A Case Report

Abstract

IntroductionRetinitis Pigmentosa (RP) is a hereditary retinal dystrophy characterized by progressive visual impairment and marked genetic heterogeneity, with more than 90 associated genes reported. Identifying disease-causing variants is important for establishing a molecular diagnosis, understanding inheritance patterns, and guiding genetic counseling and management. This case report aimed to characterize the clinical and molecular findings in individuals with RP and to identify genetic variants potentially associated with their phenotype using next-generation sequencing (NGS).Case presentationTwo individuals (IV-7 and IV-6) underwent premarital genetic screening, which revealed they are first cousins because their parents are siblings. The female carrier (IV-7) reported gradual vision loss and flashes, while the male carrier (IV-6) showed bone-spicule pigmentation in the retina. Night blindness was noted in earlier generations.DiscussionComprehensive genetic analysis identified a pathogenic frameshift variant in the RP1 gene (c.4242_4243delTA), consistent with an autosomal dominant inheritance. A Variant of Uncertain Significance (VUS) was also observed in the ZNF408 gene (c.1889G>A), though its clinical impact is still unknown. These findings highlight the challenges of genetic diagnosis in RP, the need for thorough testing, and the role of genetic counseling, especially in premarital screening. The RP finding provides a molecular explanation for the familial RP phenotype and supports the suspected inheritance pattern, whereas the ZNF408 VUS requires further evidence before a disease association can be established. These findings demonstrate the value of comprehensive genetic testing in clarifying the molecular diagnosis and inheritance pattern of RP, particularly in the context of premarital genetic testing screening.ConclusionRP is a rare disorder driven by autosomal dominant mutations. Identifying RP1 variant types using next-generation sequencing (NGS)-based testing for accurate diagnosis, and linking them to existing literature, can play a crucial role in managing and counseling RP patients.