title: Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases?
abstract: A number of human hereditary neuromuscular and neurodegenerative disorders are caused by the expansion of trinucleotide repeats within certain genes. The molecular mechanisms that underlie these expansions are not yet known. We have analyzed six trinucleotide repeat-containing loci [spinocerebellar ataxias (SCA1, SCA3, SCA8), dentatorubral-pallidoluysian atrophy (DRPLA), Huntington chorea (HD) and fragile X syndrome (FRAXA)] in myotonic dystrophy type 1 (DM1) patients (n = 52). As controls, we analyzed two groups of subjects: healthy control subjects (n =133), and a group of patients with non-triplet neuromuscular diseases (n = 68) caused by point mutations, deletions or duplications (spinal muscular atrophy, Charcot-Marie-Tooth disease, type 1A, hereditary neuropathy with liability to pressure palsies, and Duchenne and Becker muscular dystrophy). Allele frequency distributions for all tested loci were similar in these three groups with the exception of the SCA1 locus. In DM1 patients, the SCA1 allele with 31 CAG repeats account for 40.4% of all chromosomes tested, which is significantly higher than in two other groups (11.3% in healthy controls and 6.6% in the group of non-triplet diseased patients; P < 0.001, Fisher's exact test). This is consistent with our previous findings in HD patients. The absence of this association in non-triplet diseases as well as in healthy controls could indicate a possible role of this SCA1 allele with 31 repeats in triplet diseases. Here we discuss a possible role of the SCA1 region in pathological trinucleotide repeat expansions.
authors.affiliation: Faculty of Biology, University of Belgrade, Belgrade, Yugoslavia.
authors.forename: D
authors.initials: D
authors.lastname: Savić
authors.forename: I
authors.initials: I
authors.lastname: Topisirović
authors.forename: M
authors.initials: M
authors.lastname: Keckarević
authors.forename: D
authors.initials: D
authors.lastname: Keckarević
authors.forename: T
authors.initials: T
authors.lastname: Major
authors.forename: B
authors.initials: B
authors.lastname: Culjković
authors.forename: O
authors.initials: O
authors.lastname: Stojković
authors.forename: V
authors.initials: V
authors.lastname: Rakocević-Stojanović
authors.forename: J
authors.initials: J
authors.lastname: Mladenović
authors.forename: S
authors.initials: S
authors.lastname: Todorović
authors.forename: S
authors.initials: S
authors.lastname: Apostolski
authors.forename: S
authors.initials: S
authors.lastname: Romac
mesh_terms: D000483:Alleles; D000067696:Ataxin-1; D000067528:Ataxins; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012016:Reference Values; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D004247:DNA