Analysis of the C9orf72 Gene in Patients with Amyotrophic Lateral Sclerosis in Spain and Different Populations Worldwide
Por:
Garcia-Redondo, A, Dols-Icardo, O, Rojas-Garcia, R, Esteban-Perez, J, Cordero-Vazquez, P, Munoz-Blanco, JL, Catalina, I, Gonzalez-Munoz, M, Varona, L, Sarasola, E, Povedano, M, Sevilla, T, Guerrero, A, Pardo, J, de Munain, AL, Marquez-Infante, C, de Rivera, FJR, Pastor, P, Jerico, I, de Arcaya, AA, Mora, JS, Clarimon, J
Publicada:
1 ene 2013
Resumen:
A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) can cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). We assessed its frequency in 781 sporadic ALS (sALS) and 155 familial ALS (fALS) cases, and in 248 Spanish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 Ceph Europeans from Utah (CEU), 170 Yoruba Africans, 81 Han Chinese, and 85 Japanese subjects. The C9orf72 expansion was present in 27.1% of fALS and 3.2% of sALS. Mutation carriers showed lower age at onset (P = 0.04), shorter survival (P = 0.02), greater co-occurrence of FTD (P = 8.2 x 10(-5)), and more family history of ALS (P = 1.4 x 10(-20)), than noncarriers. No association between alleles within the normal range and the risk of ALS was found (P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Yoruba Africans, 8.9% CEU, 3.9% Japanese, and 1.6% Han Chinese chromosomes. Hum Mutat 34:79-82, 2013. (C) 2012 Wiley Periodicals, Inc.
Filiaciones:
Garcia-Redondo, A:
Hosp 12 Octubre, Inst Invest Biomed, ALS Unit, Dept Neurol, E-28041 Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Valencia, Spain
Dols-Icardo, O:
Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona 08025, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Rojas-Garcia, R:
Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona 08025, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Esteban-Perez, J:
Hosp 12 Octubre, Inst Invest Biomed, ALS Unit, Dept Neurol, E-28041 Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Valencia, Spain
Cordero-Vazquez, P:
Hosp 12 Octubre, Inst Invest Biomed, ALS Unit, Dept Neurol, E-28041 Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Valencia, Spain
Munoz-Blanco, JL:
Hosp Univ Gregorio Maranon, Dept Neurol, ALS Unit, Madrid, Spain
Catalina, I:
Hosp Univ Gregorio Maranon, Dept Neurol, ALS Unit, Madrid, Spain
Gonzalez-Munoz, M:
Hosp Carlos III, ALS Unit, Dept Immunol, Madrid, Spain
Varona, L:
Hosp Univ Basurto, Dept Neurol, Bilbao, Spain
Hosp Univ Basurto, Dept Genet, Bilbao, Spain
Sarasola, E:
Hosp Univ Basurto, Dept Neurol, Bilbao, Spain
Hosp Univ Basurto, Dept Genet, Bilbao, Spain
Povedano, M:
Bellvitge Hosp, Dept Neurol, Barcelona, Spain
Sevilla, T:
Hosp La Fe, Dept Neurol, E-46009 Valencia, Spain
Guerrero, A:
Hosp Clin Univ San Carlos, ALS Unit, Madrid, Spain
Pardo, J:
Clin Hosp Santiago Compostela, SERGAS, Dept Neurol, Santiago De Compostela, Spain
de Munain, AL:
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Hosp Univ Donostia, Dept Neurol, Neurosci Area, Biodonostia Hlth Res Inst, San Sebastian, Spain
Marquez-Infante, C:
Hosp Univ Virgen del Rocio, Dept Neurol, Seville, Spain
de Rivera, FJR:
Hosp Univ La Paz, Dept Neurol, ALS Unit, Madrid, Spain
Pastor, P:
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
Univ Navarra Med Sch, Univ Navarra Clin, Ctr Appl Med Res, Neurogenet Lab,Div Neurosci, Pamplona, Spain
Univ Navarra Med Sch, Univ Navarra Clin, Dept Neurol, Pamplona, Spain
Jerico, I:
Complejo Hosp Navarra, Dept Neurol, Pamplona, Spain
de Arcaya, AA:
Hosp Univ Araba Txagorritxu, Dept Neurol, Vitoria, Spain
Mora, JS:
Hosp Carlos III, ALS Unit, Dept Neurol, Madrid, Spain
Clarimon, J:
Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona 08025, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain
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