Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations.
Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations.
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DOI：
10.1007/s10048-015-0460-2
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发表时间：
2016-01
期刊：
影响因子：
2.2
通讯作者：
Agrawal PB
中科院分区：
文献类型：
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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
已知KCNA 1基因突变可引起发作性共济失调/肌震颤综合征1型（EA 1）。在这里，我们描述了两个家庭与独特的介绍谁参加了IRB批准的研究，广泛的表型，并进行全外显子组测序（WES）。家族1诊断为多个受影响个体的突然体力消耗引发的孤立性cataemia，具有异质性神经学结果。所有入选的受影响成员均携带KCNA 1 c.941T>C（p.I314T）突变。家族2有一名8岁的肌肉痉挛伴强直患者，WES显示先前报告的KCNA 1 c.677C>G（p.T226R）杂合错义突变，证实了EA 1的诊断，但无共济失调。WES确定了KCNA 1的变异，解释了两种表型，扩大了与该基因突变相关的疾病的表型谱。KCNA 1突变应考虑在所有年龄段的患者与发作性神经系统表型，即使共济失调不存在。这是一个例子，说明基因组学方法的力量，以确定致病突变的未知基因负责异质性疾病。
Mutations in the KCNA1 gene are known to cause episodic ataxia/myokymia syndrome type 1 (EA1). Here, we describe two families with unique presentations who were enrolled in an IRB-approved study, extensively phenotyped, and whole exome sequencing (WES) performed. Family 1 had a diagnosis of isolated cataplexy triggered by sudden physical exertion in multiple affected individuals with heterogeneous neurological findings. All enrolled affected members carried a KCNA1 c.941T>C (p.I314T) mutation. Family 2 had an 8-year-old patient with muscle spasms with rigidity for whom WES revealed a previously reported heterozygous missense mutation in KCNA1 c.677C>G (p.T226R), confirming the diagnosis of EA1 without ataxia. WES identified variants in KCNA1 that explain both phenotypes expanding the phenotypic spectrum of diseases associated with mutations of this gene. KCNA1 mutations should be considered in patients of all ages with episodic neurological phenotypes, even when ataxia is not present. This is an example of the power of genomic approaches to identify pathogenic mutations in unsuspected genes responsible for heterogeneous diseases.