DNAJC13 genetic variants in parkinsonism

• Published in: Movement disorders 2015-02, Vol.30 (2), p.273-278
• Main Authors: Gustavsson, Emil K., Trinh, Joanne, Guella, Ilaria, Vilariño-Güell, Carles, Appel-Cresswell, Silke, Stoessl, A. Jon, Tsui, Joseph K, McKeown, Martin, Rajput, Alex, Rajput, Ali H., Aasly, Jan O., Farrer, Matthew J.
• Format: Article
• Language: English
• Subjects: Age of Onset; DNAJC13; Female; Gene Frequency - genetics; Genetic Predisposition to Disease; genetics; Genotype; Humans; Male; Molecular Chaperones - genetics; Movement disorders; Mutation, Missense - genetics; mutations; NGS; Parkinson Disease - diagnosis; Parkinson Disease - genetics; Parkinsonian Disorders - diagnosis; Parkinsonian Disorders - genetics; parkinsonism
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.26064

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. Conclusion 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. © 2014 International Parkinson and Movement Disorder Society