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 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 +15 more
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TLDR
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.About:
This article is published in Cell.The article was published on 1996-11-01 and is currently open access. It has received 2264 citations till now. The article focuses on the topics: Familial hemiplegic migraine & Spinocerebellar ataxia type 6.read more
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Genes involved in hereditary ataxias
TL;DR: Observations in transgenic mice and in human post-mortem tissue suggest that the extended proteins are transported into the nucleus of neurons where they form intranuclear inclusions that disrupt normal nuclear function.
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Migraine and Epilepsy: A Focus on Overlapping Clinical, Pathophysiological, Molecular, and Therapeutic Aspects
Marino Muxfeldt Bianchin,Renata Gomes Londero,José Eduardo Lima,Marcelo E. Bigal,Marcelo E. Bigal +4 more
TL;DR: The relationship between migraine and epilepsy is reviewed, focusing on clinical aspects and some recent pathophysiological and molecular studies.
Journal ArticleDOI
Functional Implications of a Novel EA2 Mutation in the P/Q-Type Calcium Channel
TL;DR: A novel H1736L missense mutation in the CACNA1A gene associated with the EA2 phenotype is identified and it is shown that the mutation affects several channel properties, including reduced current density, increased rate of inactivation, and a shift in the voltage dependence of activation to more positive values.
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A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort
L Baumber,Christina Sjöstrand,M. Leone,H. Harty,Gennaro Bussone,Jan Hillert,Richard C. Trembath,Michael Bjørn Russell +7 more
TL;DR: Cluster headache is a complex genetic disorder, with possible phenotypic and genetic heterogeneity compounding attempts at gene identification, and potential linkage was identified at four possible disease loci in Danish kindreds, yet no single chromosome location generated a lod or NPL score of recognized significance.
Journal ArticleDOI
Mutations in the KCNA1 gene associated with episodic ataxia type-1 syndrome impair heteromeric voltage-gated K+ channel function
TL;DR: The results demonstrate that human Kv1.2 and KV1.1 subunits coassemble to form a novel channel with distinct gating properties that are altered profoundly by EA‐1 mutations, thus uncovering novel physiopathogenetic mechanisms of episodic ataxia type‐1 myokymia syndrome.
References
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A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
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TL;DR: The Huntington's disease mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.
Journal ArticleDOI
Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction
TL;DR: It is found that most single base changes in up to 200-base fragments could be detected as mobility shifts and the interspersed repetitive sequences of human, Alu repeats are highly polymorphic.
Journal ArticleDOI
Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.
Harry T. Orr,Ming Yi Chung,Sandro Banfi,Thomas J. Kwiatkowski,Antonio Servadio,Arthur L. Beaudet,Alanna E. McCall,Lisa A. Duvick,Laura P.W. Ranum,Huda Y. Zoghbi +9 more
TL;DR: There is a direct correlation between the size of the (CAG)n repeat expansion and the age–of–onset of SCA1, with larger alleles occurring in juvenile cases.