Familial hemiplegic migraine: involvement of a calcium neuronal channel.
Neurologia
; 12 Suppl 5: 31-7, 1997 Dec.
Article
em En
| MEDLINE
| ID: mdl-9436352
ABSTRACT
A gene for familial hemiplegic migraine (FHM), a subtype of migraine with aura, has been assigned to chromosome 19p13. In this region we identified a brain-specific P/Q-type calcium channel alpha 1A-subunit gene, CACNL1A4, with 47 exons covering 300 kb. Sequencing of all exons and their flanking surroundings revealed polymorphic variations, including a (CA)n-repeat, and a (CAG)n-repeat in the 3'-UTR. In FHM patients, we found four different missense mutations in conserved functional domains. One of the mutations has occurred on two different haplotypes in unrelated FHM families. Moreover, in episodic ataxia type-2 (EA-2), we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. Involvement of this FHM locus in migraine with and without aura was demonstrated by sib-pair analysis. We showed an increase of shared marker alleles of locus D19S394, which is tightly linked to the gene. The association between the alpha 1A calcium channel and FHM, and the increase of shared alleles in migraine affected sib-pairs, have uncovered a new pathway for the pathophysiology of migraine. This finding may provide a rationale for the development of specific prophylactic therapy for migraine and other (paroxysmal) cerebral disorders.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
/
Hemiplegia
/
Transtornos de Enxaqueca
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article