First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in familial hemiplegic migraine.
Familial hemiplegic migraine (FHM) is a rare autosomal-dominant subtype of migraine with aura, associated with hemiparesis during the aura. Here we describe a unique FHM family in which two novel allelic missense mutations in the Na,K-ATPase gene ATP1A2 segregate in the proband with hemiplegic migraine. Both mutations show reduced penetrance in family members of the proband. Cellular survival assays revealed Na,K-ATPase dysfunction for both ATP1A2 mutants, indicating that both mutations are disease causative. This is the first case of compound heterozygosity for any of the known FHM genes.
Vanmolkot
Kaate R J
KR
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Stam
Anine H
AH
Raman
Ashok
A
Koenderink
Jan B
JB
de Vries
Boukje
B
van den Boogerd
Eelke H
EH
van Vark
Judith
J
van den Heuvel
Jeroen J M W
JJ
Bajaj
Nin
N
Terwindt
Gisela M
GM
Haan
Joost
J
Frants
Rune R
RR
Ferrari
Michel D
MD
van den Maagdenberg
Arn M J M
AM
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D020325:Migraine with Aura / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase