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 journalArticle

1944 Citations (Scopus)

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

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Migraine with Aura
Exons
Genes
Mutation
3' Untranslated Regions
Chromosomes
Brain
Channelopathies
Migraine without Aura
Reading Frames
Missense Mutation
Haplotypes
Type 2 Episodic Ataxia

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Ophoff, R. A., Terwindt, G. M., Vergouwe, M. N., Van Eijk, R., Oefner, P. J., Hoffman, S. M. G., ... Frants, R. R. (1996). Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell, 87(3), 543-552. https://doi.org/10.1016/S0092-8674(00)81373-2

Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. / Ophoff, Roel A.; Terwindt, Gisela M.; Vergouwe, Monique N.; Van Eijk, Ronald; Oefner, Peter J.; Hoffman, Susan M G; Lamerdin, Jane E.; Mohrenweiser, Harvey W.; Bulman, Dennis E.; Ferrari, Maurizio; Haan, Joost; Lindhout, Dick; Van Ommen, Gert Jan B; Hofker, Marten H.; Ferrari, Michel D.; Frants, Rune R.

In: Cell, Vol. 87, No. 3, 01.11.1996, p. 543-552.

Research output: Contribution to journalArticle

Ophoff, RA, Terwindt, GM, Vergouwe, MN, Van Eijk, R, Oefner, PJ, Hoffman, SMG, Lamerdin, JE, Mohrenweiser, HW, Bulman, DE, Ferrari, M, Haan, J, Lindhout, D, Van Ommen, GJB, Hofker, MH, Ferrari, MD & Frants, RR 1996, 'Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4', Cell, vol. 87, no. 3, pp. 543-552. https://doi.org/10.1016/S0092-8674(00)81373-2
Ophoff RA, Terwindt GM, Vergouwe MN, Van Eijk R, Oefner PJ, Hoffman SMG et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996 Nov 1;87(3):543-552. https://doi.org/10.1016/S0092-8674(00)81373-2
Ophoff, Roel A. ; Terwindt, Gisela M. ; Vergouwe, Monique N. ; Van Eijk, Ronald ; Oefner, Peter J. ; Hoffman, Susan M G ; Lamerdin, Jane E. ; Mohrenweiser, Harvey W. ; Bulman, Dennis E. ; Ferrari, Maurizio ; Haan, Joost ; Lindhout, Dick ; Van Ommen, Gert Jan B ; Hofker, Marten H. ; Ferrari, Michel D. ; Frants, Rune R. / Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. In: Cell. 1996 ; Vol. 87, No. 3. pp. 543-552.
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