Amino acid changes in the amino terminus of the Na,K-adenosine triphosphatase alpha-2 subunit associated to familial and sporadic hemiplegic migraine.

Abstract	Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura inherited with an autosomal dominant pattern. Here, we report the genetic analysis of four families and one sporadic case with hemiplegic migraine (HM) in whom we searched for mutations in the three genes associated with the disease CACNA1A, ATP1A2 and SCN1A. Two novel amino acid changes p.Arg65Trp and p.Tyr9Asn, in the Na,K-adenosine triphosphatase (ATPase) alpha-2 subunit encoded by the ATP1A2 gene, were found in one FHM family and in the sporadic case, respectively. These mutations are peculiar for their location in the extreme N-terminus, an uncommon mutation target in this protein. Low frequency of migraine attacks in all our mutant patients with low complexity of the associated aura symptoms in the sporadic case is also observed. Besides the two novel mutations, the data here reported confirm the involvement of ATP1A2 gene in the sporadic form of HM, while the negative results on the other families tested for all genes known in HM strengthen the hypothesis of the existence of at least another locus involved in FHM.
Authors	A Tonelli, A Gallanti, A Bersano, V Cardin, E Ballabio, G Airoldi, F Redaelli, L Candelise, N Bresolin, M T Bassi
Journal	Clinical genetics (Clin Genet) Vol. 72 Issue 6 Pg. 517-23 (Dec 2007) ISSN: 0009-9163 [Print] Denmark
PMID	17877748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CACNA1A protein, human Calcium Channels NAV1.1 Voltage-Gated Sodium Channel Nerve Tissue Proteins SCN1A protein, human Sodium Channels DNA ATP1A2 protein, human Sodium-Potassium-Exchanging ATPase
Topics	Adult Aged Amino Acid Sequence Amino Acid Substitution Base Sequence Calcium Channels (genetics) DNA (genetics) DNA Mutational Analysis Female Genes, Dominant Humans Male Middle Aged Migraine with Aura (enzymology, genetics) Models, Molecular Molecular Sequence Data NAV1.1 Voltage-Gated Sodium Channel Nerve Tissue Proteins (genetics) Pedigree Protein Structure, Tertiary Sequence Homology, Amino Acid Sodium Channels (genetics) Sodium-Potassium-Exchanging ATPase (chemistry, genetics)

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