Analysis of the C9orf72 Gene in Patients with Amyotrophic Lateral Sclerosis in Spain and Different Populations Worldwide

被引：78

作者：

Garcia-Redondo, Alberto ^{[1
,2
]}

Dols-Icardo, Oriol ^{[3
,4
]}

Rojas-Garcia, Ricard ^{[3
,4
]}

Esteban-Perez, Jesus ^{[1
,2
]}

Cordero-Vazquez, Pilar ^{[1
,2
]}

Luis Munoz-Blanco, Jose ^{[5
]}

Catalina, Irene ^{[5
]}

Gonzalez-Munoz, Miguel ^{[6
]}

Varona, Luis ^{[7
,8
]}

Sarasola, Esther ^{[7
,8
]}

Povedano, Monica ^{[9
]}

Sevilla, Teresa ^{[10
]}

Guerrero, Antonio ^{[11
]}

Pardo, Julio ^{[12
]}

Lopez de Munain, Adolfo ^{[4
,13
]}

Marquez-Infante, Celedonio ^{[14
]}

Javier Rodriguez de Rivera, Francisco ^{[15
]}

Pastor, Pau ^{[4
,16
,17
]}

Jerico, Ivonne ^{[18
]}

Alvarez de Arcaya, Amaya ^{[19
]}

Mora, Jesus S. ^{[20
]}

Clarimon, Jordi ^{[3
,4
]}

机构：

[1] Hosp 12 Octubre, Inst Invest Biomed, ALS Unit, Dept Neurol, E-28041 Madrid, Spain

[2] Ctr Biomed Network Res Rare Dis CIBERER, Valencia, Spain

[3] Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona 08025, Spain

[4] Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain

[5] Hosp Univ Gregorio Maranon, Dept Neurol, ALS Unit, Madrid, Spain

[6] Hosp Carlos III, ALS Unit, Dept Immunol, Madrid, Spain

[7] Hosp Univ Basurto, Dept Neurol, Bilbao, Spain

[8] Hosp Univ Basurto, Dept Genet, Bilbao, Spain

[9] Bellvitge Hosp, Dept Neurol, Barcelona, Spain

[10] Hosp La Fe, Dept Neurol, E-46009 Valencia, Spain

[11] Hosp Clin Univ San Carlos, ALS Unit, Madrid, Spain

[12] Clin Hosp Santiago Compostela, SERGAS, Dept Neurol, Santiago De Compostela, Spain

[13] Hosp Univ Donostia, Dept Neurol, Neurosci Area, Biodonostia Hlth Res Inst, San Sebastian, Spain

[14] Hosp Univ Virgen del Rocio, Dept Neurol, Seville, Spain

[15] Hosp Univ La Paz, Dept Neurol, ALS Unit, Madrid, Spain

[16] Univ Navarra Med Sch, Univ Navarra Clin, Ctr Appl Med Res, Neurogenet Lab,Div Neurosci, Pamplona, Spain

[17] Univ Navarra Med Sch, Univ Navarra Clin, Dept Neurol, Pamplona, Spain

[18] Complejo Hosp Navarra, Dept Neurol, Pamplona, Spain

[19] Hosp Univ Araba Txagorritxu, Dept Neurol, Vitoria, Spain

[20] Hosp Carlos III, ALS Unit, Dept Neurol, Madrid, Spain

来源：

HUMAN MUTATION | 2013年 / 34卷 / 01期

关键词：

amyotrophic lateral sclerosis; C9orf72; frontotemporal dementia; expansion mutation; HEXANUCLEOTIDE REPEAT EXPANSION; CLINICAL CHARACTERISTICS;

D O I：

10.1002/humu.22211

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：79 / 82

页数：4

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