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

Roel A. Ophoff, Gisela M. Terwindt, Monique N. Vergouwe, Ronald Van Eijk, Peter J. Oefner, Susan M G Hoffman, Jane E. Lamerdin, Harvey W. Mohrenweiser, Dennis E. Bulman, Maurizio Ferrari, Joost Haan, Dick Lindhout, Gert Jan B Van Ommen, Marten H. Hofker, Michel D. Ferrari, Rune R. Frants

Research output: Contribution to journalArticlepeer-review

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 α1-subunit gene, CACNLIA4, 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.

Original languageEnglish
Pages (from-to)543-552
Number of pages10
JournalCell
Volume87
Issue number3
DOIs
Publication statusPublished - Nov 1 1996

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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