A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic migraine type 2.
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 alpha2 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.
Kaunisto
M A
MA
Biomedicum Helsinki, Research Program in Molecular Medicine, University of Helsinki, Helsinki, Finland. mari.kaunisto@hus.fi
Harno
H
H
Vanmolkot
K R J
KR
Gargus
J J
JJ
Sun
G
G
Hämäläinen
E
E
Liukkonen
E
E
Kallela
M
M
van den Maagdenberg
A M J M
AM
Frants
R R
RR
Färkkilä
M
M
Palotie
A
A
Wessman
M
M
D000595:Amino Acid Sequence; D002878:Chromosomes, Human, Pair 1; D005192:Family Health; D005260:Female; D005387:Finland; D005787:Gene Frequency; D008040:Genetic Linkage; D006239:Haplotypes; D006429:Hemiplegia / Q000235:genetics*; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase