OGFOD1 – Parkinson Disease

A recent exome study in a Mediterranean genetic isolate from Sardinia has nominated OGFOD1 as a candidate risk gene for Parkinson disease (PMID:25294124). In this study, exome sequencing of 100 unrelated PD patients identified several novel, moderately rare variants that were enriched in patients compared to controls, with at least five patients harboring variants in OGFOD1. Although these findings were supported by a robust case‑control design and replication in additional samples totaling nearly 6,000 individuals (PMID:25294124), the candidate association did not reach genome‑wide significance and remains to be fully validated.

Genetic evidence further indicates that the variants in OGFOD1 are rare, but detailed segregation data in familial cases have not been reported. Hence, the available data derive principally from case‑control analyses that, while promising, do not yet meet the threshold for conclusive clinical validation. In addition, the identified variants span a spectrum of coding changes, although no individual HGVS‐formatted variant description is provided in the primary report.

Functional support for a role of OGFOD1 comes from complementary studies in yeast, where the ortholog Tpa1p was shown to participate in mRNA translation termination, deadenylation, and decay (PMID:16809762). These assays suggest that perturbations in mRNA regulatory processes may underlie pathogenic mechanisms. However, direct evidence linking these functional abnormalities to the neurodegenerative phenotype in Parkinson disease remains limited.

Overall, the integration of genetic and functional data supports a tentative role for OGFOD1 in Parkinson disease, albeit with limited validity. The gene‐disease association is classified as limited due to the candidate status of the genetic findings, absence of segregation data, and a lack of definitive mechanistic insights directly in neuronal models. Additional investigations are required to definitively establish the clinical utility of OGFOD1 in diagnostic settings.

Key Take‑home: While OGFOD1 represents an interesting candidate for Parkinson disease risk, further genetic and functional validation is essential before its routine clinical application.

References

• Neurogenetics • 2015 • An exome study of Parkinson's disease in Sardinia, a Mediterranean genetic isolate PMID:25294124
• Molecular and Cellular Biology • 2006 • Tpa1p is part of an mRNP complex that influences translation termination, mRNA deadenylation, and mRNA turnover in Saccharomyces cerevisiae PMID:16809762

Evidence Based Scoring (AI generated)