[Genetics of migraine]

Abstract

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.