PRCD and Retinitis Pigmentosa

PRCD, a gene implicated in retinal degeneration, has been robustly associated with retinitis pigmentosa. Multiple independent studies have demonstrated that variants in PRCD underlie an autosomal recessive form of the disorder, with clinical findings such as bull's eye maculopathy being a characteristic feature (PMID:20507925). The evidence encompasses detailed case reports and founder mutation studies that have identified PRCD alterations in diverse populations.

Genetic evidence from several reports indicates that a recurrent nonsense variant, c.52C>T (p.Arg18Ter), is present in affected individuals and segregates with disease in multiple families (PMID:20507925; PMID:24992209). In addition to this, other diverse mutations including missense and frameshift changes have been reported, further broadening the variant spectrum associated with retinitis pigmentosa. This genetic consistency solidifies the autosomal recessive inheritance pattern and supports a strong gene‑disease association.

Segregation studies have further substantiated this association with evidence of multiple affected relatives carrying the pathogenic variants. One landmark study reported a founder mutation in 18 patients from nine distinct families (PMID:20507925), highlighting not only the familial aggregation but also the reliability of these findings across independent cohorts.

The variant spectrum for PRCD includes several mutation classes. The recurrent variant c.52C>T (p.Arg18Ter) is consistently observed and serves as a genetic marker for the disorder. Notably, these variants have been identified in independent case reports as well as larger multi‐patient studies, which reinforces the validity of these genetic findings. Use of the standardized HGVS nomenclature further aids in uniform reporting for diagnostic and research applications.

Functional studies provide compelling mechanistic insights into PRCD pathogenicity. Experimental assays have demonstrated that the native PRCD protein is secreted via the ER/Golgi‑dependent pathway, a process that is disrupted by key mutations. For example, studies have shown that while the p.P25T mutation does not alter secretion, other mutations such as p.C2Y and p.Arg17Cys compromise protein stability and proper localization (PMID:24992209, PMID:27613864, PMID:36142714). These findings are concordant with the clinical phenotype observed in retinitis pigmentosa patients.

While one study noted that the p.P25T mutation had a minimal effect on secretion, the aggregate genetic and functional evidence overwhelmingly supports a pathogenic role for PRCD in retinal disease. Conflicting functional nuances do not detract from the overall strong association; rather, they underscore the complexity of the molecular mechanisms involved.

In conclusion, the integration of robust genetic data with detailed functional analyses confirms that mutations in PRCD cause autosomal recessive retinitis pigmentosa. The consistency across case reports, segregation studies, and experimental findings provides clinicians and researchers with a firm basis for diagnostic decision‑making and potential therapeutic development.

Key take‑home sentence: The comprehensive evidence linking PRCD variants, particularly the recurrent c.52C>T (p.Arg18Ter) mutation, to retinitis pigmentosa affirms its clinical utility as a diagnostic marker and a target for future interventions.

References

• Journal of medical genetics • 2010 • Identification of a prevalent founder mutation in an Israeli Muslim Arab village confirms the role of PRCD in the aetiology of retinitis pigmentosa in humans PMID:20507925
• Experimental eye research • 2014 • The progressive rod‑cone degeneration (PRCD) protein is secreted through the conventional ER/Golgi‑dependent pathway PMID:24992209
• The Journal of biological chemistry • 2016 • Palmitoylation of Progressive Rod‑Cone Degeneration (PRCD) Regulates Protein Stability and Localization PMID:27613864
• International journal of molecular sciences • 2022 • R17C Mutation in Photoreceptor Disc‑Specific Protein, PRCD, Results in Additional Lipidation Altering Protein Stability and Subcellular Localization PMID:36142714

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