title: Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan.
abstract: 16q-ADCA (OMIM no. 117210) is an autosomal dominant spinocerebellar ataxia (AD-SCA) characterized by late-onset pure cerebellar ataxia and -16C>T substitution of the puratrophin-1 gene. Recently, a series of single-nucleotide polymorphisms (haplotype block) were found to be specific to 16q-ADCA. We screened patients with ataxia and found 62 patients, including four homozygotes who carry the C-T substitution of the puratrophin-1 gene. By further analysis of the patients with the haplotype block, we observed a single-founder effect for 16q-ADCA, even in patients who are supposed to be sporadic late cortical cerebellar atrophy (LCCA). We also observed slippage mutations of microsatellite markers, GATA01 and 17 msm, in the pedigrees. We compared the clinical course of 16q-ADCA in heterozygotes and homozygotes with the haplotype block and observed no apparent gene dosage effect. 16q-ADCA accounts for 27% of AD-SCAs and is the most frequent AD-SCA in South Kyushu, Japan.
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Ryuki
authors.initials: R
authors.lastname: Hirano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okubo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Maki
authors.forename: Shimon
authors.initials: S
authors.lastname: Ishida
authors.forename: Masahito
authors.initials: M
authors.lastname: Suehara
authors.forename: Youichi
authors.initials: Y
authors.lastname: Hokezu
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Arimura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005799:Genes, Dominant; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology*; D014910:Wheelchairs