Ducros A
Service de neurologie, hôpital Lariboisière, Paris, France.
Pathol Biol (Paris). 2000 Sep;48(7):658-62.
Two large family studies have recently demonstrated that migraine with or without aura is an hereditary condition. The most likely mode of transmission is polygenic, which renders the identification of the various implicated genes very difficult. Familial hemiplegic migraine, the sole variety of migraine to have a mendelian, autosomal dominant mode of inheritance, thus represents a unique tool to identify strong candidate genes, which implication will be tested in the more common forms of migraine. A first gene, CACNA1A, localised on chromosome 19 and coding for the main subunit of P/Q type neuronal calcium channels, is implicated in 50% of hemiplegic migraine families. A second gene, localized on chromosome 1, but still unidentified, is implicated in 20% of families. Finally, the existence of at least a third gene has been demonstrated. Better understanding of the genetical mechanisms of migraine now requires the determine of how the CACNA1A mutations produce hemiplegic migraine attacks. Moreover, identification of the two other hemiplegic migraine genes is needed to establish if they also encode ion channels. Finally, the exact role of these genes in the more common forms of migraine has to be clarified.
最近两项大型家族研究表明,有无先兆的偏头痛均为遗传性疾病。最可能的遗传方式是多基因遗传,这使得识别各种相关基因非常困难。家族性偏瘫性偏头痛是偏头痛的唯一一种具有孟德尔常染色体显性遗传模式的类型,因此它是识别强候选基因的独特工具,这些基因的关联性将在更常见的偏头痛类型中进行测试。第一个基因是CACNA1A,位于19号染色体上,编码P/Q型神经元钙通道的主要亚基,在50%的偏瘫性偏头痛家族中与之相关。第二个基因位于1号染色体上,但仍未确定,在20%的家族中与之相关。最后,已证明至少存在第三个基因。现在,要更好地理解偏头痛的遗传机制,需要确定CACNA1A突变如何引发偏瘫性偏头痛发作。此外,还需要识别另外两个偏瘫性偏头痛基因,以确定它们是否也编码离子通道。最后,必须阐明这些基因在更常见的偏头痛类型中的确切作用。