DNAJC13 genetic variants in parkinsonism.
BACKGROUND
A novel mutation (p.N855S) in DNAJC13 has been linked to familial, late-onset Lewy body parkinsonism in a Dutch-German-Russian Mennonite multi-incident kindred.


METHODS
DNAJC13 was sequenced in 201 patients with parkinsonism and 194 controls from Canada. Rare (minor allele frequency < 0.01) missense variants identified in patients were genotyped in two Parkinson's disease case-controls cohorts.


RESULTS
Eighteen rare missense mutations were identified; four were observed in controls, three were observed in both patients and controls, and eleven were identified only in patients. Subsequent genotyping showed p.E1740Q and p.L2170W to be more frequent in patients, and p.R1516H being more frequent in controls. Additionally, p.P336A, p.V722L, p.N855S, p.R1266Q were seen in one patient each, and p.T1895M was found in two patients.


CONCLUSIONS
Although the contribution of rare genetic variation in DNAJC13 to parkinsonisms remains to be further elucidated, this study suggests that, in addition to p.N855S, other rare variants might affect disease susceptibility.
Djavad Mowafaghian Centre for Brain Health, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, St. Olav's Hospital, Trondheim, Norway.
Emil K
EK
Gustavsson
Joanne
J
Trinh
Ilaria
I
Guella
Carles
C
Vilariño-Güell
Silke
S
Appel-Cresswell
A Jon
AJ
Stoessl
Joseph K
JK
Tsui
Martin
M
McKeown
Alex
A
Rajput
Ali H
AH
Rajput
Jan O
JO
Aasly
Matthew J
MJ
Farrer
D017668:Age of Onset; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics*
C507525:DNAJC13 protein, human; D018832:Molecular Chaperones
DNAJC13; NGS; genetics; mutations; parkinsonism