A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano.
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.
Ohata
Takako
T
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.
Yoshida
Kunihiro
K
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.
Sakai
Haruya
H
Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Hamanoue
Haruka
H
Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Mizuguchi
Takeshi
T
Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Shimizu
Yusaku
Y
Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Okano
Tomomi
T
Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Takada
Fumio
F
Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, 228-8555, Japan.
Ishikawa
Kinya
K
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.
Mizusawa
Hidehiro
H
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.
Yoshiura
Ko-Ichiro
KI
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Fukushima
Yoshimitsu
Y
Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Ikeda
Shu-Ichi
SI
Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Matsumoto
Naomichi
N
Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
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
D020121:5' Untranslated Regions; D020662:Guanine Nucleotide Exchange Factors; C503982:PLEKHG4 protein, human; D013049:Spectrin