A sleep modulated Channelopathy: a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine
A sleep modulated Channelopathy: a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine
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DOI：
10.1186/s12883-019-1491-3
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发表时间：
2019-10-22
期刊：
影响因子：
2.6
通讯作者：
Atwal, Paldeep S.
中科院分区：
文献类型：
--
作者：
Ahuja, Abhimanyu S.;Rozen, Todd D.;Atwal, Paldeep S.
背景描述了一例睡眠减轻的发作性共济失调2型患者，其具有一种新的CACNA1a致病变异，并提供了与睡眠反应性偏头痛的可能联系。病例介绍1例26岁女性，反复发作头晕、恶心、呕吐、共济失调和构音障碍，诊断为前庭偏头痛。她发作的独特之处在于，如果她能睡着15分钟，咒语就会消失。然而，如果她保持清醒，袭击将有增无减。经推定诊断为发作性共济失调2型，她在服用乙酰唑胺后没有发作，没有复发。基因检测发现19号染色体上CACNA1A有一个新的致病变异体。该致病变异体在文献中未见报道，建议通过引入提前终止密码子来截断CACNA1A多肽。结论报道1例发作性共济失调2型患者，其CACNA1a基因存在新的致病变异体。有趣的是，患者的症状会在睡眠中完全缓解，这表明这是一种睡眠调节的经络病。睡眠可以潜在地改变这种致病变异的机制是假设的。研究表明，睡眠与缓解偏头痛有潜在联系。对这种新的致病变异的进一步研究可能有助于我们了解睡眠不仅可以调节发作性共济失调2型，而且还可以调节偏头痛。
Background To describe a patient with sleep alleviated episodic ataxia type 2 with a novel CACNA1A pathogenic variant and provide a possible link to sleep responsive migraine. Case presentation A 26-year-old woman with recurrent attacks of dizziness, nausea, vomiting, ataxia and dysarthria presented for a possible diagnosis of vestibular migraine. Unique to her attacks was if she could fall asleep for as little as 15 min the spells would subside. If however she remained awake the attacks would continue unabated. A presumed diagnosis of episodic ataxia type 2 was made and she became attack free on acetazolamide without recurrence. Genetic testing demonstrated a novel pathogenic variant in CACNA1A on chromosome 19. This pathogenic variant has not been previously reported in the literature and is suggested to truncate the CACNA1A polypeptide by introducing a premature stop codon. Conclusion A case of episodic ataxia type 2 with a novel pathogenic variant in CACNA1A is described. Interestingly, the patient's symptoms would completely alleviate with sleep which suggests a sleep modulated channelopathy. The mechanisms by which sleep could potentially alter this pathogenic variant are hypothesized. A potential link to sleep alleviated migraine is suggested. Further study of this novel pathogenic variant may help us understand not only how sleep can modulate episodic ataxia type 2, but also migraine.