[From gene to disease; familial hemiplegic migraine as a result of mutations in a sodium-potassium pump gene].
Familial hemiplegic migraine (FHM) is a rare, autosomal dominant subtype of migraine, associated in half of the families with mutations in the CACNA1A gene located on chromosome 19p13, which encodes the Cav2.1-subunit of brain-specific P/Q-type calcium channels. Recently, mutations in a second gene, ATP1A2 on chromosome 1q23, which encodes a sodium-potassium exchange pump subunit, have been identified. The first functional studies indicate that A TP1A2 FHM mutations result in a loss of function of the pump, leading to an increase in extracellular potassium. This is known to evoke cortical spreading depression, the underlying mechanism of migraine aura.
Kors
E E
EE
Afd. Neurologie, Leids Universitair Medisch Centrum, Postbus 9600, 2300 RC Leiden.
Vanmolkot
K R J
KR
Haan
J
J
van den Maagdenberg
A M J M
AM
Frants
R R
RR
Ferrari
M D
MD
D015220:Calcium Channels / Q000235:genetics*; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002888:Chromosomes, Human, Pair 19; D020022:Genetic Predisposition to Disease; D006801:Humans; D020325:Migraine with Aura / Q000235:genetics*; D009154:Mutation; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D000254:Sodium-Potassium-Exchanging ATPase; C105656:CACNA1A protein, human; C498531:ATP1A2 protein, human