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.
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.
Authors: O Lorenzo-Betancor; K Ogaki; A I Soto-Ortolaza; C Labbe; R L Walton; A J Strongosky; J A van Gerpen; R J Uitti; P J McLean; W Springer; J Siuda; G Opala; A Krygowska-Wajs; M Barcikowska; K Czyzewski; A McCarthy; T Lynch; A Puschmann; I Rektorova; Y Sanotsky; C Vilariño-Güell; M J Farrer; T J Ferman; B F Boeve; R C Petersen; J E Parisi; N R Graff-Radford; D W Dickson; Z K Wszolek; O A Ross Journal: Eur J Neurol Date: 2015-09 Impact factor: 6.089
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Authors: Emil K Gustavsson; Joanne Trinh; Marna McKenzie; Stephanie Bortnick; Maria Skaalum Petersen; Matthew J Farrer; Jan O Aasly Journal: Mov Disord Clin Pract Date: 2017-05-23
Authors: Christina Zarouchlioti; David A Parfitt; Wenwen Li; Lauren M Gittings; Michael E Cheetham Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-01-19 Impact factor: 6.237