Analysis of the C9orf72 Gene in Patients with Amyotrophic Lateral Sclerosis in Spain and Different Populations Worldwide
Open accessAbstract
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.
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Age-, sex-, race-, and ethnicity-based variations; the frequency of comorbidities; and the effects of genetic diversity must always be kept in mind, as observed already in AD and ALS, but also within the FTD field.
“age‐, sex‐, race‐, and ethnicity‐based variations; the frequency of comorbidities; and the effects of genetic diversity must always be kept in mind, as observed already in AD and ALS, 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 but also within the FTD field. 158 , 159 , 160”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [148]
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- Authors
- García-Redondo, A., Dols-Icardo, O., Rojas-García, R., Esteban-Pérez, J., Cordero-Vázquez, P., Muñoz-Blanco, J. L., Catalina, I., González-Muñoz, M., Varona, L., Sarasola, E., Povedano, M., Sevilla, T., Guerrero, A., Pardo, J., de Munain, A. L., Márquez-Infante, C., de Rivera, F. J. R., Pastor, P., Jericó, I., de Arcaya, A. Á., Mora, J. S., Clarimón, J., The C9ORF72 Spanish Study Group, Gonzalo-Martínez, J. F., Juárez-Rufián, A., Atencia, G., Jiménez-Bautista, R., Morán, Y., Mascías, J., Hernández-Barral, M., Kapetanovic, S., García-Barcina, M., Alcalá, C., Vela, Á., Ramírez-Ramos, C., Galán, L., Pérez-Tur, J., Quintáns, B., Sobrido, M. J., Fernández-Torrón, R., Poza, J. J., Gorostidi, A., Paradas, C., Villoslada, P., Larrodé, P., Capablo, J. L., Pascual-Calvet, J., Goñi, M., Morgado, Y., Guitart, M., Moreno-Laguna, S., Rueda, A., Martín-Estefanía, C., Cemillán, C., Blesa, R., & Lleó, A.
- Affiliations
- Research Institute Hospital 12 de Octubre (ES)
- Department of Neurology; ALS Unit, Hospital Universita rio Gregorio Marañón; Madrid; Spain
- Hospital General Universitario Gregorio Marañón (ES)
- Department of Immunology; ALS Unit, Hospital Carlos III; Madrid; Spain
- Hospital de Basurto (ES)
- Department of Neurology; Hospital de Bellvitge; Barcelona; Spain
- Hospital Universitari i Politècnic La Fe (ES)
- Hospital Clínico San Carlos (ES)
- Servicio Gallego de Salud (ES)
- Department of Neurology; Hospital Universitario Virgen del Rocío; Sevilla; Spain
- Department of Neurology; ALS Unit, Hospital Universitario La Paz; Madrid; Spain
- Complejo Hospitalario de Navarra (ES)
- Department of Neurology; Hospital Universitario Araba-Txagorritxu; Vitoria-Gasteiz; Spain
- Carlos III Hospital (ES)
- Hospital de Sant Pau (ES)
- Corresponding author
- Clarimón, Jordi
- ORCID
- Venue
- Human Mutation
- Publisher
- Wiley
- Published
- 2012-10-11
- Volume
- 34
- Issue
- 1
- Pages
- 79-82
- ISSN
- 1059-7794 (ISSN-L)
- OpenAlex
- W1982638189
- Cited by
- 96
- References
- 18
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 8 · 2015: 14 · 2014: 9 · 2013: 15 · 2012: 1
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion)
- RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- C9orf72, hexanucleotide repeat expansion, amyotrophic lateral sclerosis, frontotemporal dementia, founder haplotype, sporadic ALS, familial ALS, mutation carrier frequency, age of onset, survival, family history (medicine), genetic risk, population comparison, CEU, Han Chinese, Japanese
- MeSH terms
- C9orf72 Protein, Africa, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, China, DNA Mutational Analysis, Ethnicity, Europe, Female, Gene Frequency, Haplotypes, Heterozygote, Humans, Japan, Male, Mutation, Proteins, Spain, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, DNA Repeat Expansion, Asian People, Kaplan-Meier Estimate
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