• Hiroyuki Ishiura, Yuji Takahashi, Jun Mitsui, Sohei Yoshida, Tameko Kihira, Yasumasa Kokubo, Shigeki Kuzuhara, Laura P W Ranum, Tomoko Tamaoki, Yaeko Ichikawa, Hidetoshi Date, Jun Goto, and Shoji Tsuji.
• Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
• Arch. Neurol. 2012 Sep 1;69(9):1154-8.

BackgroundIn the Kii peninsula of Japan, high prevalences of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex have been reported. There are 2 major foci with a high prevalence, which include the southernmost region neighboring the Koza River (Kozagawa and Kushimoto towns in Wakayama prefecture) and the Hohara district (Mie prefecture).ObjectiveTo delineate the molecular basis of ALS in the Kii peninsula of Japan, we analyzed hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene, which has recently been identified as a frequent cause of ALS and frontotemporal dementia in the white population.DesignCase series.SettingUniversity hospitals.PatientsTwenty-one patients (1 familial patient and 20 sporadic patients) with ALS from Wakayama prefecture, and 16 patients with ALS and 16 patients with parkinsonism-dementia complex originating from Mie prefecture surveyed in 1994 through 2011 were enrolled in the study. In addition, 40 probands with familial ALS and 217 sporadic patients with ALS recruited from other areas of Japan were also enrolled in this study.Main Outcome MeasuresAfter screening by repeat-primed polymerase chain reaction, Southern blot hybridization analysis was performed to confirm the expanded alleles.ResultsWe identified 3 patients with ALS (20%) with the repeat expansion in 1 of the 2 disease foci. The proportion is significantly higher than those in other regions in Japan. Detailed haplotype analyses revealed an extended shared haplotype in the 3 patients with ALS, suggesting a founder effect.ConclusionsOur findings indicate that the repeat expansion partly accounts for the high prevalence of ALS in the Kii peninsula.

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