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Eur J Hum Genet. 2015 Jun;23(6):887-8. doi: 10.1038/ejhg.2014.164. Epub 2014 Aug 13.

VPS35 and DNAJC13 disease-causing variants in essential tremor.

Author information

1
Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada.
2
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
3
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
4
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Abstract

Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog (VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring disease-causing variants for Parkinson disease (PD). Owing to the suggested clinical, pathological and genetic overlap between PD and essential tremor (ET) we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N)) (rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients of European descent, and microsatellite markers were used to define the disease haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients. Both patients appear to share the disease haplotype previously reported. ET patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed. Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G (p.(N855S)) represents the first disease-causing variant identified in both, and suggests the regulation of clathrin dynamics and endosomal trafficking in the pathophysiology of a subset of ET patients.

PMID:
25118025
PMCID:
PMC4795043
DOI:
10.1038/ejhg.2014.164
[Indexed for MEDLINE]
Free PMC Article

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