TRIM10 – Parkinson Disease

TRIM10, encoded by HGNC:10072, has emerged as a candidate gene in the context of Parkinson disease (MONDO_0005180). Genetic analyses in a large Chinese early-onset Parkinson disease (EOPD) cohort (743 probands (PMID:34419804)) have identified rare variants with a minor allele frequency below 0.01, including the variant c.194G>A (p.Arg65His). This variant, detected through exome sequencing, was nominally associated with EOPD and contributed to an expanded mutation spectrum for Parkinson disease.

A subsequent genome‑wide pleiotropy study further supported the involvement of TRIM10 by replicating its association in a NeuroX dataset comprising 6927 PD cases and 6108 controls (PMID:28586827). In this study, TRIM10 was confirmed alongside other established PD risk genes, lending additional credence to its role in disease predisposition. Although the association for TRIM10 is modest on a per‑variant basis, replication across independent datasets strengthens the overall genetic signal.

The aggregate genetic evidence for TRIM10 is derived primarily from case‑control studies that did not incorporate extensive multi‑generational segregation analysis. The absence of detailed familial segregation data is a limitation; however, the recurrence of the c.194G>A (p.Arg65His) variant in unrelated probands supports a moderate level of clinical validity. The current evidence aligns with a moderate ClinGen gene‑disease association tier, reflecting both the statistical association and the need for further segregation data.

Functional studies specific to TRIM10 are currently lacking. While no direct experimental assays have been performed to interrogate TRIM10’s pathogenic mechanism, insights from related TRIM family proteins imply a potential role in neuronal regulation and immune modulation. This indirect evidence suggests that TRIM10 may impact cellular pathways relevant to PD, although dedicated functional validation remains necessary.

In summary, the integrated genetic data support a moderate association between TRIM10 and Parkinson disease. The nominal genetic association identified in a large cohort, alongside replication in an independent study, underpins the potential diagnostic utility of TRIM10 in PD assessments. Further studies, including family‐based segregation analyses and targeted functional assays, will be crucial to fully elucidate the gene’s role in disease pathology.

Key take‐home: Despite limited functional data, TRIM10 represents a promising genetic marker that could enhance clinical diagnostic precision for Parkinson disease by complementing existing genetic and imaging modalities.

References

• Parkinsonism & related disorders • 2021 • Genetic analysis of TRIM family genes for early-onset Parkinson's disease in Chinese population PMID:34419804
• JAMA neurology • 2017 • Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases PMID:28586827

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