TY - JOUR
T1 - Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4
AU - Ophoff, Roel A.
AU - Terwindt, Gisela M.
AU - Vergouwe, Monique N.
AU - Van Eijk, Ronald
AU - Oefner, Peter J.
AU - Hoffman, Susan M.G.
AU - Lamerdin, Jane E.
AU - Mohrenweiser, Harvey W.
AU - Bulman, Dennis E.
AU - Ferrari, Maurizio
AU - Haan, Joost
AU - Lindhout, Dick
AU - Van Ommen, Gert Jan B.
AU - Hofker, Marten H.
AU - Ferrari, Michel D.
AU - Frants, Rune R.
N1 - Funding Information:
The authors wish to thank Steve Peroutka (Menlo Park) for providing DNA samples of family US-P. Angelika Hahn and Donald Lewis (London, Ontario) and Paola Carrera and Laura Vismara (Milan) are acknowledged for their contribution in characterization of the EA-2 families, and the Italian FHM families, respectively. Michel van Geel and Richard Lemmers are acknowlegded for their technical assistance in exon trapping and RNA isolations. We also thank Riccardo Fodde, Lodewijk Sandkuijl, and Cisca Wijmenga for their valuable discussions and critical comments on the manuscript. This work has been supported by the Phoenix Foundation (R. A. O.) and The Netherlands Organization for Scientific Research (NWO) (number 950-10-615; G. M. T.). D. E. B. is a Scholar of the MRC and his work is funded by the MRC. The work of M. F. is funded by Theleton-Italy, no. 179. Work performed by the Lawrence Livermore National Laboratory (LLNL) under auspices of the U.S. Department of Energy, under contract no. W-7405-Eng-48.
PY - 1996/11/1
Y1 - 1996/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=16044370232&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81373-2
DO - 10.1016/S0092-8674(00)81373-2
M3 - Article
C2 - 8898206
AN - SCOPUS:16044370232
SN - 0092-8674
VL - 87
SP - 543
EP - 552
JO - Cell
JF - Cell
IS - 3
ER -