BACKGROUND: In 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). OBJECTIVE: To 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. DESIGN: Case series. SETTING: University hospitals. PATIENTS: Twenty-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 MEASURES: After screening by repeat-primed polymerase chain reaction, Southern blot hybridization analysis was performed to confirm the expanded alleles. RESULTS: We 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. CONCLUSIONS: Our findings indicate that the repeat expansion partly accounts for the high prevalence of ALS in the Kii peninsula.
BACKGROUND: In 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). OBJECTIVE: To 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. DESIGN: Case series. SETTING: University hospitals. PATIENTS: Twenty-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 MEASURES: After screening by repeat-primed polymerase chain reaction, Southern blot hybridization analysis was performed to confirm the expanded alleles. RESULTS: We 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. CONCLUSIONS: Our findings indicate that the repeat expansion partly accounts for the high prevalence of ALS in the Kii peninsula.
Authors: Marka van Blitterswijk; Matthew C Baker; Mariely DeJesus-Hernandez; Roberta Ghidoni; Luisa Benussi; Elizabeth Finger; Ging-Yuek R Hsiung; Brendan J Kelley; Melissa E Murray; Nicola J Rutherford; Patricia E Brown; Thomas Ravenscroft; Bianca Mullen; Peter E A Ash; Kevin F Bieniek; Kimmo J Hatanpaa; Anna Karydas; Elisabeth McCarty Wood; Giovanni Coppola; Eileen H Bigio; Carol Lippa; Michael J Strong; Thomas G Beach; David S Knopman; Edward D Huey; Marsel Mesulam; Thomas Bird; Charles L White; Andrew Kertesz; Dan H Geschwind; Vivianna M Van Deerlin; Ronald C Petersen; Giuliano Binetti; Bruce L Miller; Leonard Petrucelli; Zbigniew K Wszolek; Kevin B Boylan; Neill R Graff-Radford; Ian R Mackenzie; Bradley F Boeve; Dennis W Dickson; Rosa Rademakers Journal: Neurology Date: 2013-09-11 Impact factor: 9.910
Authors: Zhengrui Xi; Marka van Blitterswijk; Ming Zhang; Philip McGoldrick; Jesse R McLean; Yana Yunusova; Erin Knock; Danielle Moreno; Christine Sato; Paul M McKeever; Raphael Schneider; Julia Keith; Nicolae Petrescu; Paul Fraser; Maria Carmela Tartaglia; Matthew C Baker; Neill R Graff-Radford; Kevin B Boylan; Dennis W Dickson; Ian R Mackenzie; Rosa Rademakers; Janice Robertson; Lorne Zinman; Ekaterina Rogaeva Journal: Am J Hum Genet Date: 2015-05-21 Impact factor: 11.025
Authors: Yuji Takahashi; Yoko Fukuda; Jun Yoshimura; Atsushi Toyoda; Kari Kurppa; Hiroyoko Moritoyo; Veronique V Belzil; Patrick A Dion; Koichiro Higasa; Koichiro Doi; Hiroyuki Ishiura; Jun Mitsui; Hidetoshi Date; Budrul Ahsan; Takashi Matsukawa; Yaeko Ichikawa; Takashi Moritoyo; Mayumi Ikoma; Tsukasa Hashimoto; Fumiharu Kimura; Shigeo Murayama; Osamu Onodera; Masatoyo Nishizawa; Mari Yoshida; Naoki Atsuta; Gen Sobue; Jennifer A Fifita; Kelly L Williams; Ian P Blair; Garth A Nicholson; Paloma Gonzalez-Perez; Robert H Brown; Masahiro Nomoto; Klaus Elenius; Guy A Rouleau; Asao Fujiyama; Shinichi Morishita; Jun Goto; Shoji Tsuji Journal: Am J Hum Genet Date: 2013-10-10 Impact factor: 11.025
Authors: Erika N Guerrero; Haibo Wang; Joy Mitra; Pavana M Hegde; Sara E Stowell; Nicole F Liachko; Brian C Kraemer; Ralph M Garruto; K S Rao; Muralidhar L Hegde Journal: Prog Neurobiol Date: 2016-09-28 Impact factor: 11.685
Authors: Beth A Dombroski; Douglas R Galasko; Ignacio F Mata; Cyrus P Zabetian; Ulla-Katrina Craig; Ralph M Garruto; Kiyomitsu Oyanagi; Gerard D Schellenberg Journal: JAMA Neurol Date: 2013-06 Impact factor: 18.302