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.
Mov Disord. 2015 Feb;30(2):273-8. doi: 10.1002/mds.26064. Epub 2014 Nov 12.
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.
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.
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.
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.
在一个荷兰-德国-俄罗斯门诺派多起事件家族中，DNAJC13 的一种新型突变（p.N855S）与家族性、迟发性路易体帕金森病有关。
对来自加拿大的 201 名帕金森病患者和 194 名对照者进行了 DNAJC13 测序。在患者中发现的罕见（次要等位基因频率<0.01）错义变异在两个帕金森病病例对照队列中进行了基因分型。
鉴定出 18 种罕见的错义突变；其中 4 种在对照中观察到，3 种在患者和对照中均观察到，11 种仅在患者中观察到。随后的基因分型显示 p.E1740Q 和 p.L2170W 在患者中更为常见，而 p.R1516H 在对照中更为常见。此外，p.P336A、p.V722L、p.N855S、p.R1266Q 各在一名患者中出现，p.T1895M 在两名患者中出现。
尽管 DNAJC13 中的罕见遗传变异对帕金森病的贡献仍有待进一步阐明，但本研究表明，除了 p.N855S 外，其他罕见变异也可能影响疾病易感性。
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