罕见但相关：评估帕金森病中肌张力障碍相关基因的变异
Rare but Relevant: Assessing Variants in Dystonia-linked Genes in Parkinson's Disease.
作者信息
Lange Lara M, Fang Zih-Hua, Screven Laurel, Tan Ai Huey, Alcalay Roy N, Amouri Rim, Bovenzi Roberta, Fenn Matilda, Frost Joshua L I, Jankovic Joseph, Jasaityte Simona, Jaunmuktane Zane, Jeon Beomseok, Keller Sarmiento Ignacio Juan, Krüger Rejko, Kuhlenbäumer Gregor, Lin Chin-Hsien, Pavelka Lukas, Periñan Maria Teresa, Ben Sassi Samia, Schirinzi Tommaso, Shin Jung Hwan, Shulman Joshua M, Tay Yi Wen, Uitti Ryan, Warner Tom, Wszolek Zbigniew K, Wu Lesley, Wu Ruey-Meei, Zeuner Kirsten E, Blauwendraat Cornelis, Singleton Andrew, Mencacci Niccolò E, Morris Huw R, Lim Shen-Yang, Lohmann Katja, Klein Christine
机构信息
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
出版信息
medRxiv. 2025 Jul 11:2025.07.10.25330831. doi: 10.1101/2025.07.10.25330831.
BACKGROUND
Dystonia and Parkinson's disease (PD) show clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.
OBJECTIVE
To assess the frequency of dystonia-linked pathogenic variants in PD.
METHODS
We screened sequencing data from 15,738 individuals (7,851 PD, 4,287 atypical parkinsonism, and 3,600 unaffected) from GP2 and AMP-PD for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.
RESULTS
Pathogenic variants were only identified in PD patients. Forty-five PD individuals (0.57%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most frequently in , followed by .
CONCLUSION
Though rare, pathogenic variants in dystonia-linked genes are present in clinically and pathologically diagnosed PD. Our results reinforce as a PD-relevant gene with clinical implications, while variants identified in other genes are rare and of sometimes uncertain relation to the PD phenotype.
背景
肌张力障碍与帕金森病（PD）在临床和遗传方面存在重叠，但肌张力障碍基因变异在PD中的相关性仍不明确。
目的
评估PD中与肌张力障碍相关的致病变异的频率。
方法
我们筛选了来自GP2和AMP-PD的15738名个体（7851例PD、4287例非典型帕金森综合征和3600例未受影响个体）的测序数据，以查找与孤立性肌张力障碍、肌张力障碍-帕金森综合征和肌阵挛性肌张力障碍相关基因的变异。
结果
仅在PD患者中鉴定出致病变异。45例PD个体（0.57%）在9个与肌张力障碍相关的基因中携带26种不同的（可能的）致病变异，最常见于 ，其次是 。
结论
尽管罕见，但与肌张力障碍相关的基因中的致病变异存在于临床和病理诊断的PD中。我们的结果强化了 作为一个与PD相关且具有临床意义的基因，而在其他基因中鉴定出的变异罕见，且有时与PD表型的关系不确定。
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