title: Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 Portuguese ataxia families.
abstract: The spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. To date, eight different loci causing SCA have been identified: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, SCA6, SCA7, and dentatorubropallidoluysian atrophy (DRPLA). Expansion of a CAG repeat in the disease genes has been found in five of these disorders. To estimate the relative frequencies of the SCA1, DRPLA, MJD, SCA2, and SCA6 mutations among Portuguese ataxia patients, we collected DNA samples from 48 ataxia families and performed polymerase chain reaction (PCR) amplification of the CAG repeat mutations on chromosomes 6p, 12p, 14q, 12q, and 19p, respectively. Fifty-five individuals belonging to 34 dominant families (74%) had an expanded CAG repeat at the MJD gene. In five individuals from two kindreds with a dominant pattern of inheritance (4%), an expanded CAG repeat at the SCA2 gene was found. In MJD patients, the normal allele size ranged from 13 to 41, whereas the mutant alleles contained 65 to 80 repeats. For the SCA2 patients, normal alleles had 22 or 23, while expanded alleles had between 36 and 47 CAG units. We did not find the SCA1, DRPLA, or SCA6 mutations in our group of families. The MJD mutation remains the most common cause of SCA in Portugal, while a small number of cases are caused by mutations at the SCA2 gene, and 22% are due to still unidentified genes.
authors.affiliation: Centre for Research in Neurosciences, McGill University and The Montreal General Hospital Research Institute, Québec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Silveira
authors.forename: P
authors.initials: P
authors.lastname: Coutinho
authors.forename: P
authors.initials: P
authors.lastname: Maciel
authors.forename: C
authors.initials: C
authors.lastname: Gaspar
authors.forename: S
authors.initials: S
authors.lastname: Hayes
authors.forename: A
authors.initials: A
authors.lastname: Dias
authors.forename: J
authors.initials: J
authors.lastname: Guimarães
authors.forename: L
authors.initials: L
authors.lastname: Loureiro
authors.forename: J
authors.initials: J
authors.lastname: Sequeiros
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000067696:Ataxin-1; D000067528:Ataxins; D015220:Calcium Channels / Q000235:genetics; D002877:Chromosomes, Human; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011174:Portugal; D011506:Proteins / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000235:genetics*; D018911:Trinucleotide Repeats; D020864:Calcium Channels, N-Type
chemical_list: D000067696:Ataxin-1; D000067528:Ataxins; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; C000593749:ATXN1 protein, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type