title: A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano.
abstract: The molecular bases of autosomal dominant cerebellar ataxia (ADCA) have been increasingly elucidated, but 17-50% of ADCA families still remain genetically undefined in Japan. In this study we investigated 67 genetically undefined ADCA families from the Nagano prefecture, and found that 63 patients from 51 families possessed the -16C>T change in the puratrophin-1 gene, which was recently found to be pathogenic for 16q22-linked ADCA. Most patients shared a common haplotype around the puratrophin-1 gene. All patients with the -16C>T change had pure cerebellar ataxia with middle-aged or later onset. Only one patient in a large, -16C>T positive family did not have this change, but still shared a narrowed haplotype with, and was clinically indistinguishable from, the other affected family members. In Nagano, 16q22-linked ADCA appears to be much more prevalent than either SCA6 or dentatorubral-pallidoluysian atrophy (DRPLA), and may explain the high frequency of spinocerebellar ataxia.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.|Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, 228-8555, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ohata
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. kyoshida@hsp.md.shinshu-u.ac.jp.|Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. kyoshida@hsp.md.shinshu-u.ac.jp.|Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. kyoshida@hsp.md.shinshu-u.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Haruya
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Hamanoue
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuguchi
authors.affiliation: Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Okano
authors.affiliation: Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, 228-8555, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Takada
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 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, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Ko-Ichiro
authors.initials: KI
authors.lastname: Yoshiura
authors.affiliation: Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Shu-Ichi
authors.initials: SI
authors.lastname: Ikeda
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D017668:Age of Onset; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007564:Japan; D017354:Point Mutation; D013049:Spectrin / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D020662:Guanine Nucleotide Exchange Factors; C503982:PLEKHG4 protein, human; D013049:Spectrin