title: Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwide.
abstract: 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.
authors.affiliation: Department of Neurology, ALS Unit, Instituto de Investigación Biomédica Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: García-Redondo
authors.forename: Oriol
authors.initials: O
authors.lastname: Dols-Icardo
authors.forename: Ricard
authors.initials: R
authors.lastname: Rojas-García
authors.forename: Jesús
authors.initials: J
authors.lastname: Esteban-Pérez
authors.forename: Pilar
authors.initials: P
authors.lastname: Cordero-Vázquez
authors.forename: José Luis
authors.initials: JL
authors.lastname: Muñoz-Blanco
authors.forename: Irene
authors.initials: I
authors.lastname: Catalina
authors.forename: Miguel
authors.initials: M
authors.lastname: González-Muñoz
authors.forename: Luis
authors.initials: L
authors.lastname: Varona
authors.forename: Esther
authors.initials: E
authors.lastname: Sarasola
authors.forename: Monica
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authors.lastname: Povedano
authors.forename: Teresa
authors.initials: T
authors.lastname: Sevilla
authors.forename: Antonio
authors.initials: A
authors.lastname: Guerrero
authors.forename: Julio
authors.initials: J
authors.lastname: Pardo
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.forename: Celedonio
authors.initials: C
authors.lastname: Márquez-Infante
authors.forename: Francisco Javier Rodríguez
authors.initials: FJ
authors.lastname: de Rivera
authors.forename: Pau
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authors.lastname: Pastor
authors.forename: Ivonne
authors.initials: I
authors.lastname: Jericó
authors.forename: Amaya Álvarez
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authors.lastname: de Arcaya
authors.forename: Jesús S
authors.initials: JS
authors.lastname: Mora
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Gonzalo-Martínez
authors.forename: Alexandra
authors.initials: A
authors.lastname: Juárez-Rufián
authors.forename: Gabriela
authors.initials: G
authors.lastname: Atencia
authors.forename: Rosario
authors.initials: R
authors.lastname: Jiménez-Bautista
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Morán
authors.forename: Javier
authors.initials: J
authors.lastname: Mascías
authors.forename: María
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authors.lastname: Hernández-Barral
authors.forename: Solange
authors.initials: S
authors.lastname: Kapetanovic
authors.forename: María
authors.initials: M
authors.lastname: García-Barcina
authors.forename: Carmen
authors.initials: C
authors.lastname: Alcalá
authors.forename: Alvaro
authors.initials: A
authors.lastname: Vela
authors.forename: Concepción
authors.initials: C
authors.lastname: Ramírez-Ramos
authors.forename: Lucía
authors.initials: L
authors.lastname: Galán
authors.forename: Jordi
authors.initials: J
authors.lastname: Pérez-Tur
authors.forename: Beatriz
authors.initials: B
authors.lastname: Quintáns
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Sobrido
authors.forename: Roberto
authors.initials: R
authors.lastname: Fernández-Torrón
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Poza
authors.forename: Ana
authors.initials: A
authors.lastname: Gorostidi
authors.forename: Carmen
authors.initials: C
authors.lastname: Paradas
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
authors.forename: Pilar
authors.initials: P
authors.lastname: Larrodé
authors.forename: José Luis
authors.initials: JL
authors.lastname: Capablo
authors.forename: Jordi
authors.initials: J
authors.lastname: Pascual-Calvet
authors.forename: Miguel
authors.initials: M
authors.lastname: Goñi
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Morgado
authors.forename: Miriam
authors.initials: M
authors.lastname: Guitart
authors.forename: Sira
authors.initials: S
authors.lastname: Moreno-Laguna
authors.forename: Almudena
authors.initials: A
authors.lastname: Rueda
authors.forename: Carlos
authors.initials: C
authors.lastname: Martín-Estefanía
authors.forename: Carlos
authors.initials: C
authors.lastname: Cemillán
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
mesh_terms: D000349:Africa / Q000208:ethnology; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D000073885:C9orf72 Protein; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D042622:DNA Repeat Expansion / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005060:Europe / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007564:Japan / Q000208:ethnology; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D013030:Spain
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins