Familial cortical myoclonus with a mutation in NOL3.
Familial cortical myoclonus with a mutation in NOL3.
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DOI：
10.1002/ana.23666
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发表时间：
2012-08
影响因子：
11.2
通讯作者：
Ptacek, Louis J.
中科院分区：
文献类型：
--
作者：
Russell, Jonathan F.;Steckley, Jamie L.;Coppola, Giovanni;Hahn, Angelika F. G.;Howard, MacKenzie A.;Kornberg, Zachary;Huang, Alden;Mirsattari, Seyed M.;Merriman, Barry;Klein, Eric;Choi, Murim;Lee, Hsien-Yang;Kirk, Andrew;Nelson-Williams, Carol;Gibson, Gillian;Baraban, Scott C.;Lifton, Richard P.;Geschwind, Daniel H.;Fu, Ying-Hui;Ptacek, Louis J.
肌阵挛的特征是突然的、短暂的不自主运动，它的存在使人虚弱。我们发现一个家系患有成人起病的皮质肌阵挛，没有相关的癫痫发作。我们进行了临床、电生理和遗传学研究，以确定这种表型。一个有肌阵挛病史的四代大家庭接受了仔细的询问、检查和电生理测试。35名家庭成员捐献了血液样本进行基因分析，包括SNP作图、微卫星连锁、靶向大规模平行测序和桑格测序。在硅胶和体外实验中，研究了该突变的功能意义。我们确定了一个加拿大门诺派家庭的11名成员，他们患有成人起病、缓慢进展、致残的多灶性肌阵挛。体感诱发电位显示肌阵挛起源于皮质。没有相关的癫痫发作。一些受严重影响的人在病程后期出现了进行性小脑性共济失调的迹象，其严重程度各不相同。该表型为常染色体显性遗传。我们证实了与染色体16q21-22.1的连锁。然后我们对关键区域的所有编码序列进行了测序，只鉴定了一个共同分离的、新颖的、非同义的突变，它位于NOL3基因中。此外，该突变被发现在体外改变了NOL3蛋白的翻译后修饰。我们认为家族性皮质肌阵挛(FCM)是一种新的运动障碍，可能由NOL3基因突变引起。进一步研究NOL3在神经生理学中的作用可能有助于揭示神经细胞膜的超兴奋性和肌阵挛及相关疾病的病理生理学。
Myoclonus is characterized by sudden, brief involuntary movements and its presence is debilitating. We identified a family suffering from adult-onset, cortical myoclonus without associated seizures. We performed clinical, electrophysiological, and genetic studies to define this phenotype. A large, four-generation family with history of myoclonus underwent careful questioning, examination, and electrophysiological testing. Thirty-five family members donated blood samples for genetic analysis, which included SNP mapping, microsatellite linkage, targeted massively parallel sequencing, and Sanger sequencing. In silico and in vitro experiments were performed to investigate functional significance of the mutation. We identified 11 members of a Canadian Mennonite family suffering from adult-onset, slowly progressive, disabling, multifocal myoclonus. Somatosensory evoked potentials indicated a cortical origin of the myoclonus. There were no associated seizures. Some severely affected individuals developed signs of progressive cerebellar ataxia of variable severity late in the course of their illness. The phenotype was inherited in an autosomal dominant fashion. We demonstrated linkage to chromosome 16q21-22.1. We then sequenced all coding sequence in the critical region, identifying only a single co-segregating, novel, nonsynonymous mutation, which resides in the gene NOL3. Furthermore, this mutation was found to alter post-translational modification of NOL3 protein in vitro. We propose that Familial Cortical Myoclonus (FCM) is a novel movement disorder that may be caused by mutation in NOL3. Further investigation of the role of NOL3 in neuronal physiology may shed light on neuronal membrane hyperexcitability and pathophysiology of myoclonus and related disorders.
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DOI：
10.1006/bbrc.2001.4306
发表时间：
2001-02-16
影响因子：
3.1
作者：
Engidawork, E;Gulesserian, T;Lubec, G
通讯作者：
Lubec, G
影响因子：
64.5
作者：
Chou, JJ;Matsuo, H;Wagner, G
通讯作者：
Wagner, G
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影响因子：
37.8
作者：
Tan, Wei-Qi;Wang, Jian-Xun;Li, Pei-Feng
通讯作者：
Li, Pei-Feng
影响因子：
9.9
作者：
Roze, E.;Apartis, E.;Vidailhet, M.
通讯作者：
Vidailhet, M.
影响因子：
7.3
作者：
Olsen, Jesper V.;Vermeulen, Michiel;Mann, Matthias
通讯作者：
Mann, Matthias