Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

Détails

ID Serval
serval:BIB_B4E051BFBF6E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.
Périodique
Journal of the Neurological Sciences
Auteur(s)
García Segarra N., Gautschi I., Mittaz-Crettol L., Kallay Zetchi C., Al-Qusairi L., Van Bemmelen M.X., Maeder P., Bonafé L., Schild L., Roulet-Perez E.
ISSN
1878-5883 (Electronic)
ISSN-L
0022-510X
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
342
Numéro
1-2
Pages
69-78
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel CaV2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant CaV2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.
Pubmed
Web of science
Création de la notice
17/06/2014 9:27
Dernière modification de la notice
20/08/2019 15:23
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