Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4
CellPublished 1 November 1996Open access
Roel A. Ophoff, Gisela M. Terwindt, Monique N. Vergouwe, Ronald van Eijk, Peter J. Oefner, Susan M.G. Hoffman
Citations2,341
SJR quartileQ1
SJR score22.61
SNIP7.62
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TL;DR
A brain-specific P/Q-type Ca2+ channel alpha1-subunit gene, CACNL1A4, covering 300 kb with 47 exons is characterized, revealing 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.
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.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
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