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VPS35 and DNAJC13 disease-causing variants in essential tremor
Alex Rajput1, Jay P Ross2, Cecily Q Bernales2
1Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada.
European Journal of Human Genetics : EJHG
|August 14, 2014
Summary
The DNAJC13 gene variant, previously linked to Parkinson disease, was found in essential tremor patients, suggesting a shared genetic link. This is the first disease-causing variant identified in both conditions, implicating endosomal trafficking in essential tremor.
Area of Science:
- Neurogenetics
- Molecular Neurology
Background:
- Parkinson disease (PD) and essential tremor (ET) share clinical, pathological, and genetic similarities.
- Exome sequencing identified VPS35 and DNAJC13 variants in PD, prompting investigation into their role in ET.
Purpose of the Study:
- To investigate the presence of disease-causing variants in VPS35 and DNAJC13 in essential tremor patients.
- To explore the potential genetic overlap between PD and ET.
Main Methods:
- Genotyping of 571 European ET patients for VPS35 c.1858G>A (p.(D620N)) and DNAJC13 c.2564A>G (p.(N855S)) variants using TaqMan probes.
- Microsatellite markers were used to define the disease haplotype in variant carriers.
Main Results:
- Two ET patients were found to harbor the DNAJC13 c.2564A>G (p.(N855S)) variant, previously identified in PD patients.
- These two patients shared the previously reported disease haplotype.
- No ET patients with the VPS35 c.1858G>A (p.(D620N)) variant were observed.
Conclusions:
- The DNAJC13 c.2564A>G (p.(N855S)) variant is the first identified disease-causing variant in both PD and ET.
- This finding suggests that clathrin dynamics and endosomal trafficking are implicated in the pathophysiology of a subset of ET patients.
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