Abstract
Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries1,2. About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache3. Although the mode of transmission is controversial4, population-based and twin studies have implicated genetic factors, especially in migraine with aura5,6. 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 α2 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.
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Acknowledgements
We thank the individuals with FHM for participating and I. Bernascone for assistance in mutation screening. This work was partially supported by the Italian Telethon Foundation and the Agarini Foundation. This work was carried out in the framework of the Italian Ministry of Research Center of Excellence in Physiopathology of Cell Differentiation.
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Fusco, M., Marconi, R., Silvestri, L. et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 33, 192–196 (2003). https://doi.org/10.1038/ng1081
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DOI: https://doi.org/10.1038/ng1081
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