title: Episodic ataxia and SCA6 within the same family due to the D302N CACNA1A gene mutation.
abstract: Several dominant mutations of CACNA1A gene were associated with at least three different allelic disorders: spino-cerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2), and familial hemiplegic migraine-1 (FHM1). It is generally thought that loss-of-function mutations are associated with EA2, gain-of-function missense mutations with FHM1, and abnormal CAG expansions with SCA6. But, overlapping features, atypical symptoms and co-occurrence of distinct phenotypes within the same family were reported. We describe a four generation family showing different phenotypes ranging from EA2 to SCA6 and carrying the p.D302N CACNA1A gene mutation. In our family the phenotypes maintained separate and gender differences corresponding to different phenotypes were observed.
authors.affiliation: Division of Neurology and Neurorehabilitation, IRCCS Istituto Auxologico Italiano, Italy. Electronic address: l.pradotto@auxologico.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Pradotto
authors.affiliation: Laboratory of Molecular Biology, IRCCS Istituto Auxologico Italiano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Mencarelli
authors.affiliation: Division of Neurology and Neurorehabilitation, IRCCS Istituto Auxologico Italiano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bigoni
authors.affiliation: Division of Neurology and Neurorehabilitation, IRCCS Istituto Auxologico Italiano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Milesi
authors.affiliation: Laboratory of Molecular Biology, IRCCS Istituto Auxologico Italiano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Blasio
authors.affiliation: Division of Neurology and Neurorehabilitation, IRCCS Istituto Auxologico Italiano, Italy; Department of Neuroscience, University of Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mauro
mesh_terms: D000293:Adolescent; D001259:Ataxia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy; D001921:Brain / Q000000981:diagnostic imaging; D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy; D055815:Young Adult; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
keywords: Acetazolamide; CACNA1A; Episodic ataxia; Gender differences; SCA6