Demos Michelle K, Macri Vincenzo, Farrell Kevin, Nelson Tanya N, Chapman Kristine, Accili Eric, Armstrong Linlea
Department of Pediatric Neurology, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.
Mov Disord. 2009 Apr 15;24(5):778-82. doi: 10.1002/mds.22467.
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 suggests that KCNA1 mutations are associated with a broader clinical phenotype, which may include persistent cerebellar dysfunction and cognitive delay.
1型发作性共济失调是一种常染色体显性疾病，其特征为共济失调发作和肌纤维颤搐。它与KCNA1电压门控钾通道基因突变有关。在本研究中，我们描述了一个具有新临床特征的家系，包括持续性小脑功能障碍、小脑萎缩和认知延迟。所有受影响的家庭成员都有肌纤维颤搐和癫痫，但只有一人有眩晕发作。其他特征包括姿势异常、发作性僵硬和虚弱。在受影响的家庭成员中鉴定出一种新的KCNA1突变（c.1222G>T），该突变在第408位将高度保守的缬氨酸替换为亮氨酸（p.Val408Leu），并发现其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，这可能包括持续性小脑功能障碍和认知延迟。
