Cell
Vol. 87, pp. 543-552, Nov. 1, 1996
Familial Hemiplegic Migraine and Episodic Ataxia
Type-2 Are Caused by Mutations in the Ca2+ Channel
Gene CACNL1A4
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.
(Cell 1996;87:543-552)
(1996;87:543-552) Roel A. Ophoff et al, MCG Department of Human
Genetics, Sylvius Laboratory, Leiden University, Wassenaarseweg 72,
2333 AL Leiden, the Netherlands. |
