CACNA1A mutation linking hemiplegic migraine and alternating hemiplegia of childhood.
Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.
de Vries
B
B
Department of Human Genetics, Leiden University Medical Centre, Leiden, Germany.
Stam
A H
AH
Beker
F
F
van den Maagdenberg
A M J M
AM
Vanmolkot
K R J
KR
Laan
Laem
L
Ginjaar
I B
IB
Frants
R R
RR
Lauffer
H
H
Haan
J
J
Haas
J P
JP
Terwindt
G M
GM
Ferrari
M D
MD
D000293:Adolescent; D015220:Calcium Channels / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006429:Hemiplegia / Q000235:genetics*; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D009154:Mutation; D014430:Twins, Monozygotic / Q000235:genetics*; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type