TY - JOUR
T1 - VPS35 and DNAJC13 disease-causing variants in essential tremor
AU - Rajput, Alex
AU - Ross, Jay P.
AU - Bernales, Cecily Q.
AU - Rayaprolu, Sruti
AU - Soto-Ortolaza, Alexandra I.
AU - Ross, Owen A.
AU - Van Gerpen, Jay
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew K.
AU - Rajput, Ali H.
AU - Vilariño-Güell, Carles
N1 - Funding Information:
Essential Tremor Foundation, and has participated in clinical trials funded by Teva (TVP-1012/501) and Merck Serono SA-Geneva (EMR 701165-024). Has also received honoraria from Teva and UCB Canada Inc. AHR receives research support from the Saskatchewan Parkinson’s Disease Foundation, Curling Classic, and PrintWest Golf Classic, and has received a travel grant from Teva. ZKW is funded by NIH NS072187 and is the Editor in Chief of Parkinsonism and Related Disorders. OAR is a member of the editorial board of PLoS ONE and American Journal of Neurodegenerative Disease and Parkinsonism and Related Disorders, and he is funded by NIH grants NS078086 and NS072187. The remaining authors declare no conflict of interest.
Funding Information:
We wish to thank the patients and families who participated in the study. This work was supported in part by The Canada Research Chair program, Vancouver Coastal Health Research Institute (CV-G), Regina Curling Classic for Parkinson research, Greystone Golf Classic for Parkinson’s, the Royal University Hospital Foundation (AR, AHR), Morris K. Udall Parkinson’s Disease Research Center of Excellence (NINDS P50 #NS072187), NINDS R01 NS078086 and the Mayo Clinic Research Program (OAR, ZKW). Additional support from the Canada Excellence Research Chair (CERC) program was provided by Matthew J Farrer.
Funding Information:
AR has received research support from the Regina Curling Classic, Greystone Classic for Parkinson’s, Inc., the Dr Ali Rajput Endowment for Parkinson’s Disease and Movement Disorders and the International
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/6/15
Y1 - 2015/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929275666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929275666&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2014.164
DO - 10.1038/ejhg.2014.164
M3 - Article
C2 - 25118025
AN - SCOPUS:84929275666
SN - 1018-4813
VL - 23
SP - 887
EP - 888
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -