Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy
Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy
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DOI：
10.1111/cge.12542
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发表时间：
2015-02-01
影响因子：
3.5
通讯作者：
Coimbra, R. L. M.
中科院分区：
文献类型：
--
作者：
Pena, S. D. J.;Coimbra, R. L. M.
我们最近在一个7岁的男孩进行了外显子组分析，他在婴儿期表现为以共济失调和肌阵挛性癫痫为特征的脑病。父母没有血缘关系，也没有家族病史。外显子组分析未显示已知与儿童癫痫发作和/或共济失调相关的基因中的任何致病性变体，包括所有已知的人类通道病。然而，我们已经确定了KCNA 2的突变，我们认为这是我们患者疾病的原因。该基因编码钾通道、电压门控、Shaker相关亚家族的一个成员，以前未被描述为人类疾病的原因，但已知小鼠中的orthopathy基因（Kcna 2）突变会引起共济失调和惊厥。突变为c.890C>A，导致氨基酸取代p.Arg297Gln，其涉及S4电压传感器中的第二个关键氨基酸。这种突变的特点是致病性的活不同的预测程序。限制性片段长度多态性分析和桑格测序证实了该突变存在于患者体内，但不存在于其父母体内，将其定性为新生。我们认为这一发现是一种新的通道病的特征。
We have recently performed exome analysis in a 7 year boy who presented in infancy with an encephalopathy characterized by ataxia and myoclonic epilepsy. Parents were not consanguineous and there was no family history of the disease. Exome analysis did not show any pathogenic variants in genes known to be associated with seizures and/or ataxia in children, including all known human channelopathies. However, we have identified a mutation in KCNA2 that we believe to be responsible for the disease in our patient. This gene, which encodes a member of the potassium channel, voltage-gated, shaker-related subfamily, has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions. The mutation is c.890C>A, leading to the amino acid substitution p.Arg297Gln, which involves the second of the critical arginines in the S4 voltage sensor. This mutation is characterized as pathogenic by live different prediction programs. RFLP analysis and Sanger sequencing confirmed the presence of the mutation in the patient, but not in his parents, characterizing it as de novo. We believe that this discovery characterizes a new channelopathy.