Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4

@article{Ophoff1996FamilialHM,
  title={Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4},
  author={Roel A. Ophoff and Gisela M. Terwindt and Monique N. Vergouwe and Ronald van Eijk and Peter J. Oefner and Susan M. G. Hoffman and Jane E. Lamerdin and Harvey W. Mohrenweiser and Dennis E. Bulman and Maurizio Ferrari and Joost Haan and Dick Lindhout and G. J. B. Ommen and Marten H. Hofker and Michel D. Ferrari and Rune R. Frants},
  journal={Cell},
  year={1996},
  volume={87},
  pages={543-552}
}
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… Expand

Paper Mentions

Interventional Clinical Trial
Episodic ataxia type 2 (EA2) is a rare familial neurological condition characterized by debilitating episodes of vertigo and imbalance. Since the serendipitous discovery of dramatic… Expand
ConditionsEpisodic Ataxia Type 2
InterventionDrug
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TLDR
The PRKCSH gene can be excluded for both FHM and EA-2, because no potential disease causing mutation was found and therefore the PRK CSH gene was excluded. Expand
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TLDR
Results confirm the localization of a gene for familial hemiplegic migraine to the short arm of chromosome 19, but locus heterogeneity not corresponding to the observed clinical heterogeneity is likely to exist. Expand
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TLDR
Linkage analysis in two large families with FPCA/-M that also demonstrated neurodegenerative pathology of the cerebellum is performed, and a CAG trinucleotide-repeat expansion was detected in one family but did not cosegregate with the disease. Expand
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TLDR
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TLDR
Two-point and multipoint lod score analyses as well as HOMOG testing provided strong evidence for genetic heterogeneity of FHM and it was established that the most likely location of the gene was within an interval of 12 cM between D 19S413 and D19S226. Expand
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TLDR
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TLDR
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TLDR
FHM linked to chromosomes 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features and in one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Expand
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TLDR
It is suggested that the hemiplegic migraine attacks and the cerebellar degeneration are linked genetically and that the eye movements are not the ischemic sequelae of recurrent migraine. Expand
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TLDR
The results indicate that the DHP-receptor alpha 1-subunit mutation causes HypoPP, and an altered excitation-contraction coupling may explain the occurrence of muscle weakness. Expand
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