title: Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.
abstract: Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries. About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache. Although the mode of transmission is controversial, population-based and twin studies have implicated genetic factors, especially in migraine with aura. 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.
authors.affiliation: Human Molecular Genetics Unit, Dibit-San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: De Fusco
authors.forename: Roberto
authors.initials: R
authors.lastname: Marconi
authors.forename: Laura
authors.initials: L
authors.lastname: Silvestri
authors.forename: Luigia
authors.initials: L
authors.lastname: Atorino
authors.forename: Luca
authors.initials: L
authors.lastname: Rampoldi
authors.forename: Letterio
authors.initials: L
authors.lastname: Morgante
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
authors.forename: Paolo
authors.initials: P
authors.lastname: Aridon
authors.forename: Giorgio
authors.initials: G
authors.lastname: Casari
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D015220:Calcium Channels / Q000235:genetics; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006238:Haploidy; D006367:HeLa Cells; D006801:Humans; D008297:Male; D020325:Migraine with Aura / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010042:Ouabain / Q000494:pharmacology; D010375:Pedigree; D010446:Peptide Fragments; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010042:Ouabain; C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase