title: Novel frameshift mutation in the CACNA1A gene causing a mixed phenotype of episodic ataxia and familiar hemiplegic migraine.
abstract: Episodic ataxia type 2 (EA2, MIM#108500) is the most common form of EA and an autosomal-dominant inherited disorder characterized by paroxysmal episodes of ataxia. The disease causative gene CACNA1A encodes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel. We report on a family with a novel mutation in the CACNA1A gene. The clinical symptoms within the family varied from the typical clinical presentation of EA2 with dysarthria, gait ataxia and oculomotor symptoms to migraine and dystonia. A novel nonsense mutation of the CACNA1A gene was identified in all affected family members and is most likely the disease causing molecular defect. The pharmacological treatment with acetazolamide (AAA) was successful in three family members so far. Treatment with AAA led to a reduction of migraine attacks and an improvement of the dystonia. This relationship confirmed the hypothesis that this novel mutation results in a heterogeneous phenotype and confutes the coincidence with common migraine. Dystonia is potentially included as a further part of the phenotype spectrum of CACNA1A gene mutations.
authors.affiliation: Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany. Electronic address: Silvia.Kinder@uniklinikum-dresden.de.
authors.forename: S
authors.initials: S
authors.lastname: Kinder
authors.affiliation: Klinik für Neurologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Ossig
authors.affiliation: Klinik für Neurologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wienecke
authors.affiliation: Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Beyer
authors.affiliation: Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von der Hagen
authors.affiliation: Klinik für Neurologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Storch
authors.affiliation: Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Smitka
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D017668:Age of Onset; D015220:Calcium Channels / Q000235:genetics*; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D004401:Dysarthria / Q000209:etiology; D004421:Dystonia / Q000209:etiology; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D008297:Male; D020325:Migraine with Aura / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D020864:Calcium Channels, N-Type
chemical_list: D000086:Acetazolamide; D015220:Calcium Channels; D002257:Carbonic Anhydrase Inhibitors; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
keywords: Acetazolamide; CACNA1A gene; Dystonia; Episodic ataxia; Familiar hemiplegic migraine