Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine

Familial hemiplegic migraine is a severe type of migraine with aura. It often includes some level of hemiparesis during migraine attacks. Researchers previously identified mutations in two genes linked to this condition. These genes are CACNA1A and ATP1A2. This study aimed to find additional genes causing familial hemiplegic migraine. They performed a genome-wide linkage analysis on two affected families. The analysis focused on ion channel genes for mutations. They discovered a new locus for familial hemiplegic migraine on chromosome 2q24. Sequencing revealed a missense mutation in the SCN1A gene. This mutation was found in three families with the migraine condition. The mutation alters the charge in the protein's hinged-lid domain. It affects the sodium channel's fast inactivation process. This study shows dysfunction in SCN1A can lead to familial hemiplegic migraine. It also highlights links between migraine and epilepsy, both paroxysmal disorders. Clinical relevance: This research suggests dysfunction in SCN1A may lead to familial hemiplegic migraine.