title: Evaluation of polyglutamine repeats in autosomal dominant Parkinson's disease.
abstract: We evaluated the contributions of various polyglutamine (polyQ) disease genes to Parkinson's disease (PD). We compared the distributions of polyQ repeat lengths in 8 common genes (ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATN1, and HTT) in 299 unrelated patients with autosomal dominant PD (ADPD) and 329 normal controls. We also analyzed the possibility of genetic interactions between ATXN1 and ATXN2, ATXN2 and ATXN3, and ATXN2 and CACNA1A. Intermediate-length polyQ expansions (>24 Qs) of ATXN2 were found in 7 ADPD patients and no controls (7/299 = 2.34% and 0/329 = 0%, respectively; p = 0.0053 < 0.05/8 after Bonferroni correction). These patients showed typical L-DOPA-responsive PD phenotypes. Conversely, no significant differences in polyQ repeat lengths were found between the ADPD patients and the controls for the other 7 genes. Our results may support the hypothesis that ATXN2 polyQ expansion is a specific predisposing factor for multiple neurodegenerative diseases.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan; Department of Neuroscience for Neurodegenerative Disorders, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.affiliation: Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.affiliation: Department of Neurology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Naka-ku, Hiroshima, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Inamizu
authors.affiliation: Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Ando
authors.affiliation: Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yuanzhe
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Department of Neurology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Naka-ku, Hiroshima, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Araki
authors.affiliation: Department of Neurology, Saitama Prefectural Rehablitation Center, Ageo-city, Saitama, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Medical Education, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ehara
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kinya
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.affiliation: Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan; Department of Neuroscience for Neurodegenerative Disorders, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000067528:Ataxins; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics*
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine
keywords: Ataxin-2; Intermediate length; Parkinson's disease; Polyglutamine; Trinucleotide repeat diseases