1. Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwide
- Author
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Miguel González-Muñoz, Catalina I, Capablo Jl, Guitart M, Ramírez-Ramos C, Márquez-Infante C, García-Barcina M, Pablo Villoslada, Ricardo Rojas-García, Hernández-Barral M, Jordi Pérez-Tur, José Luis Muñoz-Blanco, Pau Pastor, Guerrero A, Juárez-Rufián A, Julio Pardo, Varona L, Moreno-Laguna S, Teresa Sevilla, María-Jesús Sobrido, Paradas C, Ana Gorostidi, Beatriz Quintáns, Larrodé P, A. Lleo, Jesús Esteban-Pérez, de Rivera Fj, Alcalá C, López de Munain A, Goñi M, Rafael Blesa, Kapetanovic S, Cordero-Vázquez P, Poza Jj, Pascual-Calvet J, Roberto Fernandez-Torron, Morán Y, Sarasola E, Morgado Y, Gonzalo-Martínez Jf, Atencia G, Mònica Povedano, Mascías J, Cemillán C, Martín-Estefanía C, Alberto García-Redondo, Jordi Clarimón, Jiménez-Bautista R, Rueda A, de Arcaya Aá, Vela A, Ivonne Jericó, Jesus S. Mora, Galán L, Oriol Dols-Icardo, Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, and Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
- Subjects
Male ,China ,Heterozygote ,DNA Mutational Analysis ,Chromosome 9 ,Kaplan-Meier Estimate ,Biology ,Polymorphism, Single Nucleotide ,Asian People ,Gene Frequency ,Japan ,C9orf72 ,Genetics ,medicine ,Ethnicity ,Humans ,Genetic Predisposition to Disease ,Family history ,Allele ,Amyotrophic lateral sclerosis ,Genetics (clinical) ,Aged ,Aged, 80 and over ,DNA Repeat Expansion ,C9orf72 Protein ,Haplotype ,Amyotrophic Lateral Sclerosis ,Proteins ,medicine.disease ,Europe ,Haplotypes ,Spain ,Africa ,Mutation ,Female ,Trinucleotide repeat expansion ,Frontotemporal dementia - Abstract
The C9ORF72 Spanish Study Group, et al., 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. © 2012 Wiley Periodicals, Inc., We acknowledge the ALS Research Spanish Foundation (FUNDELA) and the UTE project FIMA (Spain) for their help to P.P. Contract grant sponsors: Neuromuscular Database Project, CIBERNED (PI 2010/11); MICINN (SAF2010-10434); ISCIII (PI10/00092 and EC08/00049).
- Published
- 2013