作者
Alberto García‐Redondo,Oriol Dols‐Icardo,Ricard Rojas‐García,Jesús Esteban‐Pérez,Pilar Cordero-Vázquez,José Luis Muñoz‐Blanco,Irene Catalina,Miguel González‐Muñoz,L. Varona,Esther Sarasola,Mónica Povedano,Teresa Sevilla,Antonio Guerrero,Julio Pardo,Adolfo López de Munaín,C. Márquez Infante,F. Rivera,Pau Pástor,Ivonne Jericó,Amaya Álvarez de Arcaya,Jesús S. Mora,Jordi Clarimón,Juan Francisco Gonzalo-Martínez,Alexandra Juárez-Rufián,Gabriela Atencia,Rosario Jiménez-Bautista,Yolanda Morán,Javier Mascías,María Hernández-Barral,Solange Kapetanovic,María García‐Barcina,Carmen Alcalá,Álvaro Vela,C. Ramírez-Ramos,Lucía Galán,Jordi Pérez‐Tur,Beatriz Quintáns,M.J. Sobrido,Roberto Fernández‐Torrón,Juan José Poza,Ana Gorostidi,Carmen Paradas,Pablo Villoslada,P Larrodé,J L Capablo,Jordi Pascual-Calvet,Miguel Goñi,Yolanda Blanco Morgado,Míriam Guitart,Sira Moreno-Laguna,Almudena Rueda,C Martín-Estefanía,Carlos Cemillán,Rafael Blesa,Alberto Lleó
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 × 10(-5)), and more family history of ALS (P = 1.4 × 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.