Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions.
Familial hemiplegic migraine (FHM) is a rare, severe, autosomal dominant subtype of migraine with aura. Up to 75% of FHM families have a mutation in the P/Q-type calcium channel Ca(v)2.1 subunit CACNA1A gene on chromosome 19p13. Some CACNA1A mutations also may cause epilepsy. Here, we describe novel missense mutations in the ATP1A2 Na(+),K(+)-ATPase pump gene on chromosome 1q23 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q mutation was identified in a family in which FHM and benign familial infantile convulsions partially cosegregate. In this family, all available affected family members with FHM, benign familial infantile convulsions, or both, carry the ATP1A2 mutation. Like FHM linked to 19p13, FHM linked to 1q23 also involves dysfunction of ion transportation and epilepsy is part of its phenotypic spectrum.
Vanmolkot
Kaate R J
KR
Department of Human Genetics, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
Kors
Esther E
EE
Hottenga
Jouke-Jan
JJ
Terwindt
Gisela M
GM
Haan
Joost
J
Hoefnagels
Wil A J
WA
Black
David F
DF
Sandkuijl
Lodewijk A
LA
Frants
Rune R
RR
Ferrari
Michel D
MD
van den Maagdenberg
Arn M J M
AM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D020936:Epilepsy, Benign Neonatal / Q000150:complications / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D020325:Migraine with Aura / Q000150:complications / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D013045:Species Specificity
D000254:Sodium-Potassium-Exchanging ATPase