Graves, TD and Imbrici, P and Kors, EE and Terwindt, GM and Eunson, LH and Frants, RR and Haan, J and Ferrari, MD and Goadsby, PJ and Hanna, MG and van den Maagdenberg, AMJM and Kullmann, DM (2008) Premature stop codons in a facilitating EF-hand splice variant of CaV2.1 cause episodic ataxia type 2. Neurobiology of Disease, 32 (1). pp. 10-15. DOI https://doi.org/10.1016/j.nbd.2008.06.002
Graves, TD and Imbrici, P and Kors, EE and Terwindt, GM and Eunson, LH and Frants, RR and Haan, J and Ferrari, MD and Goadsby, PJ and Hanna, MG and van den Maagdenberg, AMJM and Kullmann, DM (2008) Premature stop codons in a facilitating EF-hand splice variant of CaV2.1 cause episodic ataxia type 2. Neurobiology of Disease, 32 (1). pp. 10-15. DOI https://doi.org/10.1016/j.nbd.2008.06.002
Graves, TD and Imbrici, P and Kors, EE and Terwindt, GM and Eunson, LH and Frants, RR and Haan, J and Ferrari, MD and Goadsby, PJ and Hanna, MG and van den Maagdenberg, AMJM and Kullmann, DM (2008) Premature stop codons in a facilitating EF-hand splice variant of CaV2.1 cause episodic ataxia type 2. Neurobiology of Disease, 32 (1). pp. 10-15. DOI https://doi.org/10.1016/j.nbd.2008.06.002
Abstract
Premature stop codons in CACNA1A, which encodes the alpha(1A) subunit of neuronal P/Q-type (Ca(V)2.1) Ca(2+) channels, cause episodic ataxia type 2 (EA2). CACNA1A undergoes extensive alternative splicing, which contributes to the pharmacological and kinetic heterogeneity of Ca(V)2.1-mediated Ca(2+) currents. We identified three novel heterozygous stop codon mutations associated with EA2 in an alternately spliced exon (37A), which encodes part of an EF-hand motif required for Ca(2+)-dependent facilitation. One family had a C to G transversion (Y1854X). A dinucleotide deletion results in the same premature stop codon in a second family, and a further single nucleotide change leads to a different truncation (R1858X) in a de novo case of EA2. Expression studies of the Y1854X mutation revealed loss of Ca(V)2.1-mediated current. Because these mutations do not affect the alternate exon 37B, these findings reveal unexpected dependence of cerebellar function on intact exon 37A-containing Ca(V)2.1 channels.
Item Type: | Article |
---|---|
Uncontrolled Keywords: | EA2; Ataxia; Cerebellum; Channelopathy; Ca2+ channel; Migraine |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 11 Jan 2013 14:56 |
Last Modified: | 07 Aug 2024 16:54 |
URI: | http://repository.essex.ac.uk/id/eprint/5064 |