title: SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6.
abstract: We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85-399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as alpha(1A)-voltage-dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients.
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Masaya
authors.initials: M
authors.lastname: Oda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morino
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okada
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ito
authors.forename: Iwao
authors.initials: I
authors.lastname: Sasaki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Komure
authors.forename: Fukashi
authors.initials: F
authors.lastname: Udaka
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012016:Reference Values; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D004247:DNA; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C415906:ATXN8OS gene product, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type