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.
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands, and Department of Neurology, Dr Lütfi Kirdar State Hospital, Maltepe, Istanbul, Turkey.
Kaate R J
KR
Vanmolkot
Esther E
EE
Kors
Ulku
U
Turk
Dylsad
D
Turkdogan
Antoine
A
Keyser
Ludo A M
LA
Broos
Sima Kheradmand
SK
Kia
Jeroen J M W
JJ
van den Heuvel
David F
DF
Black
Joost
J
Haan
Rune R
RR
Frants
Virginia
V
Barone
Michel D
MD
Ferrari
Giorgio
G
Casari
Jan B
JB
Koenderink
Arn M J M
AM
van den Maagdenberg
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