title: Redefining the disease locus of 16q22.1-linked autosomal dominant cerebellar ataxia.
abstract: The 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA; Online Mendelian Inheritance in Man [OMIN] #117210) is one of the most common ADCAs in Japan. Previously, we had reported that the patients share a common haplotype by founder effect and that a C-to-T substitution (-16C>T) in the puratrophin-1 gene was strongly associated with the disease. However, recently, an exceptional patient without the substitution was reported, indicating that a true pathogenic mutation might be present elsewhere. In this study, we clarified the disease locus more definitely by the haplotype analysis of families showing pure cerebellar ataxia. In addition to microsatellite markers, the single nucleotide polymorphisms (SNPs) that we identified on the disease chromosome were examined to confirm the borders of the disease locus. The analysis of 64 families with the -16C>T substitution in the puratrophin-1 gene revealed one family showing an ancestral recombination event between SNP04 and SNP05 on the disease chromosome. The analysis of 22 families without identifiable genetic mutations revealed another family carrying the common haplotype centromeric to the puratrophin-1 gene, but lacking the -16C>T substitution in this gene. We concluded that the disease locus of 16q-ADCA was definitely confined to a 900-kb genomic region between the SNP04 and the -16C>T substitution in the puratrophin-1 gene in 16q22.1.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Amino
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. kishikawa.nuro@tmd.ac.jp.
authors.forename: Kinya
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Shuta
authors.initials: S
authors.lastname: Toru
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ishiguro
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsunemi
authors.affiliation: Department of Neurology, Musashi Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.affiliation: Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.affiliation: Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. h-mizusawa.nuro@tmd.ac.jp.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D002524:Cerebellar Ataxia / Q000235:genetics*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D013049:Spectrin / Q000235:genetics*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C503982:PLEKHG4 protein, human; D013049:Spectrin