Abstract
Familial hemiplegic migraine (FHM), a rare autosomal dominant subtype of migraine with aura, has been linked to two chromosomal loci, 19p13 and 1q23. Mutations in the Na+,K+-ATPase α2 subunit gene, ATP1A2, on 1q23 have recently been shown to cause familial hemiplegic migraine type 2 (FHM2). We sequenced the coding regions of this gene in a Finnish chromosome 1q23-linked FHM family with associated symptoms such as coma and identified a novel A1033G mutation in exon 9. This mutation results in a threonine-to-alanine substitution at codon 345. This residue is located in a highly conserved N-terminal region of the M4–5 loop of the Na+,K+-ATPase. Furthermore, the T345A mutation co-segregated with the disorder in our family and was not present in 132 healthy Finnish control individuals. For these reasons it is most likely the FHM-causing mutation in this family.
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Acknowledgements
Financial support was provided by the Research Funds of the Helsinki University Central Hospital, the Paulo Foundation, NIH ROI NS37675–02 (to A.P.), the Research Foundation of the University of Helsinki (Young Scientist’s Award, to M.A.K), the Finnish Neurology Foundation, the Biomedicum Helsinki Foundation, the Research Foundation of Orion Corporation, the Finnish Cultural Foundation, NIH RO1 MH59222 (to J.J.G), The Netherlands Organization for Scientific Research (NWO), and the European Community (to R.R.F.) and is gratefully acknowledged. We especially thank our FHM family for their devoted participation in this study. Finally, we wish to thank Dr. Kaisa Silander for her kind help with the allele frequency estimations.
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Kaunisto, M.A., Harno, H., Vanmolkot, K.R.J. et al. A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic migraine type 2. Neurogenetics 5, 141–146 (2004). https://doi.org/10.1007/s10048-004-0178-z
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DOI: https://doi.org/10.1007/s10048-004-0178-z