A Novel KCNA1 Mutation Associated with Global Delay and Persistent Cerebellar Dysfunction
A Novel KCNA1 Mutation Associated with Global Delay and Persistent Cerebellar Dysfunction
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DOI：
10.1002/mds.22467
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发表时间：
2009-04-15
影响因子：
8.6
通讯作者：
Armstrong, Linlea
中科院分区：
文献类型：
--
作者：
Demos, Michelle K.;Macri, Vincenzo;Armstrong, Linlea
发作性共济失调1型是一种常染色体显性遗传病，以发作性共济失调和肌无力为特征。它与KCNA1电压门控钾通道基因的突变有关。在本研究中，我们描述了一个具有新的临床特征的家庭，包括持续的小脑功能障碍，小脑萎缩和认知延迟。所有受影响的家庭成员都有肌动症和癫痫，但只有一个人有眩晕发作。其他特征包括姿势异常，阵发性僵硬和虚弱。在受影响的家族成员中发现了一种新的KCNA1突变（c.1222G>T），该突变将高度保守的缬氨酸替换为408位的亮氨酸（p.Val408Leu），并发现该突变增强了通道失活的能力。总之，我们的数据表明KCNA1突变与更广泛的临床表型相关，其中可能包括持续的小脑功能障碍和认知延迟。(C) 2009运动障碍学会
Episodic Ataxia Type 1 is an autosomal dominant disorder characterized by episodes of ataxia and myokymia. It is associated with mutations in the KCNA1 voltage-gated potassium channel gene. In the present study, we describe a family with novel clinical features including persistent cerebellar dysfunction, cerebellar atrophy, and cognitive delay. All affected family members have myokymia and epilepsy, but only one individual has episodes of vertigo. Additional features include postural abnormalities, episodic stiffness and weakness. A novel KCNA1 mutation (c.1222G>T) which replaces a highly conserved valine with leucine at position 408 (p.Val408Leu) was identified in affected family members, and was found to augment the ability of the channel to inactivate. Together, our data suggest that KCNA1 mutations are associated with a broader clinical phenotype, which may include persistent cerebellar dysfunction and cognitive delay. (C) 2009 Movement Disorder Society