CACNA1A

基因产物：P/Q型钙通道α1A亚基。

蛋白功能：主要在神经组织中表达，参与电压敏感型钙离子通道的组成，引起P/Q型钙电流。

相关疾病：发育性癫痫性脑病42型（部分可表现为Lennox-Gastaut综合征 ）（AD）[1，8]；发作性共济失调（AD）[2]；家族性偏瘫型偏头痛（AD）[3]；家族性偏瘫型偏头痛伴进行性小脑共济失调（AD）[4]；脊髓小脑型共济失调（AD）[5]；遗传性癫痫伴失神发作（易感基因）[6]；青少年失神癫痫[7]。

突变数据库：ClinVar数据库。

相关临床研究：PubMed数据库（PMID: 31468518 (Epilepsia. 2019); PMID: 27212419 (Pediatr Neurol. 2016)）

用药提醒：拉莫三嗪（同时有P/Q型钙通道阻滞的效果）可能对该基因突变所致的发育性癫痫性脑病有效（仅个例报道，只供参考，且该篇报道所对应的CACNA1A突变理论上讲属于功能增强型的突变可能性大，实际上不管是功能减弱型或功能增强型CACNA1A突变均可导致发育性癫痫性脑病，两者用药上可能会存在差异）[7, 8]。

讨论版块：点击进入CACNA1A基因突变讨论版块。

参考文献

1. Epi, K.C., De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.Am J Hum Genet, 2016. 99(2): p. 287-98.
2. Riant, F., et al., Large CACNA1A deletion in a family with episodic ataxia type 2.Arch Neurol, 2008. 65(6): p. 817-20.
3. Ophoff, R.A., et al., Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.Cell, 1996. 87(3): p. 543-52.
4. Ducros, A., et al., Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia.Am J Hum Genet, 1999. 64(1): p. 89-98.
5. Ishikawa, K., et al., Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.Am J Hum Genet, 1997. 61(2): p. 336-46.
6. Yalcin, O., Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies.Seizure, 2012. 21(2): p. 79-86.
7. Byers, H.M., et al., Dramatic Response After Lamotrigine in a Patient With Epileptic Encephalopathy and a De NovoCACNA1A Variant.Pediatr Neurol, 2016. 60: p. 79-82.
8. Jiang, X., et al., Both gain-of-function and loss-of-function de novo CACNA1A mutations cause severe developmental epileptic encephalopathies in the spectrum of Lennox-Gastaut syndrome.Epilepsia, 2019. 60(9): p. 1881-1894.