Two de novo mutations in the Na,K-ATPase gene ATP1A2 associated with pure familial hemiplegic migraine.
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 alpha2-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.
Vanmolkot
Kaate R J
KR
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands, and Department of Neurology, Dr Lütfi Kirdar State Hospital, Maltepe, Istanbul, Turkey.
Kors
Esther E
EE
Turk
Ulku
U
Turkdogan
Dylsad
D
Keyser
Antoine
A
Broos
Ludo A M
LA
Kia
Sima Kheradmand
SK
van den Heuvel
Jeroen J M W
JJ
Black
David F
DF
Haan
Joost
J
Frants
Rune R
RR
Barone
Virginia
V
Ferrari
Michel D
MD
Casari
Giorgio
G
Koenderink
Jan B
JB
van den Maagdenberg
Arn M J M
AM
D000595:Amino Acid Sequence; D002878:Chromosomes, Human, Pair 1; D005260:Female; D006367:HeLa Cells; D006429:Hemiplegia / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism
C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase