title: Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM.
abstract: Mutations in the brain specific P/Q type Ca2+ channel alpha1 subunit gene, CACNA1A, have been identified in three clinically distinct disorders, viz. episodic ataxia type 2 (EA-2), familial hemiplegic migraine (FHM) and spinocerebellar ataxia 6 (SCA6). For individuals with EA-2, the mutations described thus far are presumed to result in a truncated protein product. Several different missense mutations have been identified in patients with FHM. At least two of these mutations have been identified on two different chromosome 19p13 haplotypes and thus represent recurrent mutations. In the present study, we have screened several individuals for mutations in all 47 exons in the CACNA1A gene by single-strand conformation analysis. We have characterised a novel missense mutation, G5260A, in exon 32 in a family segregating for EA-2. The consequence of this mutation is an amino acid substitution at a highly conserved position within the CACNA1A gene. This represents the first point mutation not resulting in a proposed truncated protein. Furthermore, this mutation has been detected in a family member with mild clinical signs including only migraine. Additionally, a second previously identified recurrent muta tion, C2272T, in exon 16 has been discovered in a patient with FHM.
authors.affiliation: Department of Cytogenetics and Molecular Genetics Women's and Children's Hospital, North Adelaide, South Australia, Australia. kfriend@mad.adelaide.edu.au
authors.forename: K L
authors.initials: KL
authors.lastname: Friend
authors.forename: D
authors.initials: D
authors.lastname: Crimmins
authors.forename: T G
authors.initials: TG
authors.lastname: Phan
authors.forename: C M
authors.initials: CM
authors.lastname: Sue
authors.forename: A
authors.initials: A
authors.lastname: Colley
authors.forename: V S
authors.initials: VS
authors.lastname: Fung
authors.forename: J G
authors.initials: JG
authors.lastname: Morris
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: R I
authors.initials: RI
authors.lastname: Richards
mesh_terms: D000595:Amino Acid Sequence; D001259:Ataxia / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006429:Hemiplegia / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008881:Migraine Disorders / Q000150:complications / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D004247:DNA; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type