First case of compound heterozygosity in Na, K-ATPase gene ATP1A2 in familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is a rare autosomal-dominant subtype of migraine with aura, associated with hemiparesis during the aura. Here we describe a unique FHM family in which two novel allelic missense mutations in the Na,K-ATPase gene ATP1A2 segregate in the proband with hemiplegic migraine. Both mutations show reduced penetrance in family members of the proband. Cellular survival assays revealed Na,K-ATPase dysfunction for both ATP1A2 mutants, indicating that both mutations are disease causative. This is the first case of compound heterozygosity for any of the known FHM genes.