DNAJC10 – Parkinson Disease

This summary reviews the association between DNAJC10 (HGNC:24637) and Parkinson disease (MONDO_0005180) as supported by recent genetic studies in Chinese cohorts. Studies have applied both case‑control and rare variant burden analyses to evaluate the role of DNAJC family members, including DNAJC10, in early‑onset and sporadic Parkinson disease, contributing to a developing clinical picture. The statistical analyses in one study of 512 patients and 512 controls revealed that the DNAJC10 variant rs13414223 exhibited significant protective effects (PMID:27653456).

Genetic evidence is further bolstered by a mutation analysis study that identified the rare variant c.55C>A (p.Leu19Ile) in a cohort of 664 unrelated early‑onset Parkinson disease patients (PMID:32662538). Although the evidence originates primarily from case‑control analyses rather than clear multi‑family segregation data, the replication of association signals across independent studies increases confidence. The cumulative case counts and statistically significant allele frequency differences support a moderate level of gene–disease association.

In terms of inheritance, Parkinson disease is typically considered an autosomal dominant disorder for risk‐variants, and while the DNAJC10 risk allele appears to behave in a dominant fashion, explicit familial segregation data are minimal. The lack of detailed reports on affected relatives with segregating alleles limits the evaluation of intrafamilial transmission. Nonetheless, the identification of recurrent signals in independent cohorts reinforces the clinical relevance of DNAJC10 for diagnostic evaluation.

Functional insights into DNAJC10 are more limited. As a co‑chaperone and reductase, DNAJC10 likely contributes to protein quality control mechanisms and endoplasmic reticulum–associated degradation, processes which are biologically relevant to the neuronal degeneration observed in Parkinson disease. However, direct functional assays linking DNAJC10 activity to Parkinson pathology have not been reported, leaving a gap between genetic association and mechanistic validation.

Overall, integrated genetic evidence from case‑control and mutation screening studies indicates a moderate association between DNAJC10 and Parkinson disease, while functional evidence remains suggestive but limited. This synthesis supports its potential utility in diagnostic decision‑making and highlights the need for further functional studies to clarify the molecular pathways involved.

Key Take‑home Sentence: Emerging genetic associations of DNAJC10 with Parkinson disease provide moderate clinical evidence that could inform diagnosis and future research, despite the current paucity of direct functional data.

References

• Movement disorders : official journal of the Movement Disorder Society • 2020 • Mutation Analysis of DNAJC Family for Early‑Onset Parkinson's Disease in a Chinese Cohort PMID:32662538
• Scientific reports • 2016 • Systematic analysis of genetic variants in Han Chinese patients with sporadic Parkinson's disease PMID:27653456

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