SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6.
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.
Izumi
Yuishin
Y
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
Maruyama
Hirofumi
H
Oda
Masaya
M
Morino
Hiroyuki
H
Okada
Takayuki
T
Ito
Hidefumi
H
Sasaki
Iwao
I
Tanaka
Hiroyasu
H
Komure
Osamu
O
Udaka
Fukashi
F
Nakamura
Shigenobu
S
Kawakami
Hideshi
H
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
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