title: Absence of spinocerebellar ataxia type 3/Machado-Joseph disease within ataxic patients in the Czech population.
abstract: Although spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease is the most common type of SCA worldwide, we did not identify any cases of the disease amongst SCA patients in the Czech population. It has been proposed that the prevalence of large normal alleles correlates with the frequency of various types of SCA. We have therefore attempted to resolve the absence of SCA3 in our population by investigating, within 204 normal chromosomes, the frequency and nature of CAG repeats as well as two intragenic polymorphisms. We found that large normal alleles with more than 33 CAG repeats were observed at a frequency of only 0.49%. Whereas most of the expanded alleles worldwide have the CA haplotype, this was the least common (5.4%) variant observed in our study, although it was associated with a larger mean CAG repeat length (26.9). We postulate that the absence of SCA3 in the Czech population might be explained by the lack of large normal alleles and consequently a relatively small reservoir for aberrant CAG expansions at the SCA3 locus.
authors.affiliation: Neurogenetic Centre of the Institute of Biology and Medical Genetics, Department of Child Neurology, 2nd Medical Faculty of Charles University and Faculty Hospital Motol, Prague, Czech Republic. pbauer@brain.riken.go.jp
authors.forename: P O
authors.initials: PO
authors.lastname: Bauer
authors.forename: A
authors.initials: A
authors.lastname: Zumrova
authors.forename: V
authors.initials: V
authors.lastname: Matoska
authors.forename: T
authors.initials: T
authors.lastname: Marikova
authors.forename: S
authors.initials: S
authors.lastname: Krilova
authors.forename: A
authors.initials: A
authors.lastname: Boday
authors.forename: B
authors.initials: B
authors.lastname: Singh
authors.forename: P
authors.initials: P
authors.lastname: Goetz
mesh_terms: D000483:Alleles; D000067699:Ataxin-3; D018153:Czech Republic; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3