Referenced in: none

Automatically associated channels: Cav2.1

Title: Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.

Authors: R A Ophoff, G M Terwindt, M N Vergouwe, R van Eijk, P J Oefner, S M Hoffman, J E Lamerdin, H W Mohrenweiser, D E Bulman, M Ferrari, J Haan, D Lindhout, G J van Ommen, M H Hofker, M D Ferrari, R R Frants

Journal, date & volume: Cell, 1996 Nov 1 , 87, 543-52

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8898206

Abstract
Genes for familial hemiplegic migraine (FHM) and episodic ataxia type-2 (EA-2) have been mapped to chromosome 19p13. We characterized a brain-specific P/Q-type Ca2+ channel alpha1-subunit gene, CACNL1A4, covering 300 kb with 47 exons. Sequencing of all exons and their surroundings revealed polymorphic variations, including a (CA)n-repeat (D19S1150), a (CAG)n-repeat in the 3'-UTR, and different types of deleterious mutations in FHM and EA-2. In FHM, we found four different missense mutations in conserved functional domains. One mutation has occurred on two different haplotypes in unrelated FHM families. In EA-2, we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. A similar etiology may be involved in common types of migraine.