Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2
Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2
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DOI：
10.1038/ng1081
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发表时间：
2003-02-01
期刊：
影响因子：
30.8
通讯作者：
Casari, G
中科院分区：
文献类型：
--
作者：
De Fusco, M;Marconi, R;Casari, G
头痛发作和自主神经功能障碍是偏头痛的特征，偏头痛是一种非常常见的致残性疾病，在西方国家的普通人群中患病率为12%（1,2）。大约20%的偏头痛患者会经历先兆，一种视觉或感觉-运动神经功能障碍，通常先于头痛或伴随头痛。虽然传播方式存在争议(4)，但基于人群和双胞胎的研究表明遗传因素，特别是先兆偏头痛（5,6）。家族性偏瘫偏头痛是一种以先兆和部分偏瘫为特征的遗传性偏头痛。本研究表明，编码Na+/K+泵α 2亚基的ATP1A2基因突变与与染色体1q23 （OMIM 602481）相关的家族性偏瘫偏头痛2型（FHM2）有关。功能数据表明，假定的发病机制是由ATP1A2单个等位基因的功能丧失引发的。这是首次报道将Na+K+泵亚基突变与遗传疾病联系起来。
Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries(1,2). About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache(3). Although the mode of transmission is controversial(4), population-based and twin studies have implicated genetic factors, especially in migraine with aura(5,6). Familial hemiplegic migraine is a hereditary form of migraine characterized by aura and some hemiparesis. Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM 602481). Functional data indicate that the putative pathogenetic mechanism is triggered by a loss of function of a single allele of ATP1A2. This is the first report associating mutations of Na+K+ pump subunits to genetic diseases.