Abstract
Familial hemiplegic migraine (FHM) is a rare autosomal dominantly inherited subtype of migraine, in which hemiparesis occurs during the aura. The majority of the families carry mutations in the CACNA1A gene on chromosome 19p13 (FHM1). About 20% of FHM families is linked to chromosome 1q23 (FHM2), and has mutations in the ATP1A2 gene, encoding the α2-subunit of the Na,K-ATPase. Mutation analysis in a Dutch and a Turkish family with pure FHM revealed two novel de novo missense mutations, R593W and V628M, respectively. Cellular survival assays support the hypothesis that both mutations are disease-causative. The identification of the first de novo mutations underscores beyond any doubt the involvement of the ATP1A2 gene in FHM2.
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Acknowledgements
We thank Dr Thomas A Pressley (the University of Texas Medical School, Lubbock, USA) for generously providing the anti-HERED antibody. This work was supported by grants of the Netherlands Organization for Scientific Research (NWO) (903-52-291, MDF, RRF, and Vici 918.56.602, MDF), The Migraine Trust (RRF, MDF), the EU ‘EUROHEAD’ grant (LSHM-CT-2004-504837; MDF, RRF, AMJMvdM, GC), Hersenstichting (JBK, AMJMvdM) and the Center of Medical System Biology (CMSB) established by the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NGI/NWO).
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Vanmolkot, K., Kors, E., Turk, U. et al. Two de novo mutations in the Na,K-ATPase gene ATP1A2 associated with pure familial hemiplegic migraine. Eur J Hum Genet 14, 555–560 (2006). https://doi.org/10.1038/sj.ejhg.5201607
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DOI: https://doi.org/10.1038/sj.ejhg.5201607
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