Paroxysmal Movement Disorders.
Paroxysmal Movement Disorders.
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DOI：
10.3389/fneur.2021.659064
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发表时间：
2021
影响因子：
3.4
通讯作者：
Gorman KM
中科院分区：
文献类型：
--
作者：
Harvey S;King MD;Gorman KM
阵发性运动障碍(PxMD)是一组临床和遗传上不同的运动障碍，以阵发性不自主运动(肌张力障碍、运动障碍、舞蹈病和/或共济失调)为特征。在历史上，PxMD是根据临床(运动的触发因素和特征)进行分类的，这种直接的单基因检测。随着下一代测序(NGS)的出现，我们对PxMD的分类和研究方式发生了变化。下一代测序使新的基因发现(RHOBTB2，TBC1D24)成为可能，扩大了已知PxMDS基因的表型，并更好地理解了疾病机制。然而，PxMDs表现出表型多效性和遗传异质性，这使得根据临床表型预测基因具有挑战性。例如，阵发性运动性运动障碍最常见的与PRRT2的变异有关，但也与PNKD、SCN8A和SCL2A1的变异有关。目前还没有放射或生化生物标记物来区分遗传原因。即使在NGS中，诊断率也是不同的，根据研究的队列和采用的技术，诊断率从11%到51%不等。因此，与癫痫等其他神经疾病相比，很大比例的患者仍然没有得到诊断，这突显了对PxMD进行进一步基因组研究的必要性。全基因组测序、深度测序、拷贝数变异分析、深层内含子变异的检测、嵌合体和重复扩增，将提高诊断率。确定潜在的遗传原因对患者护理、改进治疗、长期预测和遗传咨询具有重要影响。本文综述了PxMDs的遗传学研究进展，并根据致病基因而不是临床表型对PxMDs进行了分类，强调了PxMDs的主要临床特征，并提供了一种PxMDs的基因检测算法。
Paroxysmal movement disorders (PxMDs) are a clinical and genetically heterogeneous group of movement disorders characterized by episodic involuntary movements (dystonia, dyskinesia, chorea and/or ataxia). Historically, PxMDs were classified clinically (triggers and characteristics of the movements) and this directed single-gene testing. With the advent of next-generation sequencing (NGS), how we classify and investigate PxMDs has been transformed. Next-generation sequencing has enabled new gene discovery (RHOBTB2, TBC1D24), expansion of phenotypes in known PxMDs genes and a better understanding of disease mechanisms. However, PxMDs exhibit phenotypic pleiotropy and genetic heterogeneity, making it challenging to predict genotype based on the clinical phenotype. For example, paroxysmal kinesigenic dyskinesia is most commonly associated with variants in PRRT2 but also variants identified in PNKD, SCN8A, and SCL2A1. There are no radiological or biochemical biomarkers to differentiate genetic causes. Even with NGS, diagnosis rates are variable, ranging from 11 to 51% depending on the cohort studied and technology employed. Thus, a large proportion of patients remain undiagnosed compared to other neurological disorders such as epilepsy, highlighting the need for further genomic research in PxMDs. Whole-genome sequencing, deep-sequencing, copy number variant analysis, detection of deep-intronic variants, mosaicism and repeat expansions, will improve diagnostic rates. Identifying the underlying genetic cause has a significant impact on patient care, modification of treatment, long-term prognostication and genetic counseling. This paper provides an update on the genetics of PxMDs, description of PxMDs classified according to causative gene rather than clinical phenotype, highlighting key clinical features and providing an algorithm for genetic testing of PxMDs.
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影响因子：
11.2
作者：
Chen, Ying-Zhang;Friedman, Jennifer R.;Chen, Dong-Hui;Chan, Guy C. -K.;Bloss, Cinnamon S.;Hisama, Fuki M.;Topol, Sarah E.;Carson, Andrew R.;Pham, Phillip H.;Bonkowski, Emily S.;Scott, Erick R.;Lee, Janel K.;Zhang, Guangfa;Oliveira, Glenn;Xu, Jian;Scott-Van Zeeland, Ashley A.;Chen, Qi;Levy, Samuel;Topol, Eric J.;Storm, Daniel;Swanson, Phillip D.;Bird, Thomas D.;Schork, Nicholas J.;Raskind, Wendy H.;Torkamani, Ali
通讯作者：
Torkamani, Ali
影响因子：
30.8
作者：
Chen, Wan-Jin;Lin, Yu;Wu, Zhi-Ying
通讯作者：
Wu, Zhi-Ying
影响因子：
2.2
作者：
Brownstein CA;Beggs AH;Rodan L;Shi J;Towne MC;Pelletier R;Cao S;Rosenberg PA;Urion DK;Picker J;Tan WH;Agrawal PB
通讯作者：
Agrawal PB
影响因子：
3.1
作者：
Battaglia, Agatino;Doccini, Viola;Carey, John C.
通讯作者：
Carey, John C.
一名患有新型 KCNMA1 变异体 K457E 的 25 岁女性的肌张力障碍状态、眼科危象和阵发性运动障碍。
DOI：
10.5334/tohm.549
发表时间：
2020-10-27
期刊：
Tremor and other hyperkinetic movements (New York, N.Y.)
影响因子：
--
作者：
Buckley C;Williams J;Munteanu T;King M;Park SM;Meredith AL;Lynch T
通讯作者：
Lynch T