title: Meiotic CAG repeat instability in spinocerebellar ataxia type 6: maternally transmitted elongation in a presumed sporadic case.
abstract: Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominantly inherited disorder characterized by cerebellar ataxia, dysarthria and nystagmus. The molecular background for the disorder is a CAG repeat expansion in the CACNA1A gene located on chromosome 19. The size of SCA6 expanded alleles is usually stable, and variation in repeat size over successive generations is rare. We report a Danish family with one case of SCA6 resembling a sporadic case of spinocerebellar ataxia. Analysis of the CACNA1A gene showed meiotic CAG repeat instability in the transmission from a 70-year-old woman with no subjective symptoms to her symptomatic son. The CAG repeat size expanded from 22 repeats in the mother to 23 repeats in the proband. This case demonstrates maternal repeat instability and clinical anticipation in a family with SCA6.
authors.affiliation: Department of Medical Biochemistry and Genetics, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Denmark.
authors.forename: Suzanne Granhøj
authors.initials: SG
authors.lastname: Lindquist
authors.forename: Anne
authors.initials: A
authors.lastname: Nørremølle
authors.forename: Lena Elisabeth
authors.initials: LE
authors.lastname: Hjermind
authors.forename: Lis
authors.initials: L
authors.lastname: Hasholt
authors.forename: Jørgen Erik
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D000368:Aged; D020132:Anticipation, Genetic; D015220:Calcium Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000208:ethnology / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type