title: VPS35 and DNAJC13 disease-causing variants in essential tremor.
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.
authors.affiliation: Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Rajput
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Ross
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Cecily Q
authors.initials: CQ
authors.lastname: Bernales
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Sruti
authors.initials: S
authors.lastname: Rayaprolu
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Soto-Ortolaza
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: van Gerpen
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.affiliation: Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C507525:DNAJC13 protein, human; D018832:Molecular Chaperones; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins