ArticleEuropean journal of human genetics : EJHG2013
The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder.
Article in European journal of human genetics : EJHG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 2 of them syntheses that pooled it.
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Who cites it
115 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A meta-analysis of observational studies of the association between chronic occupational exposure to lead and amyotrophic lateral sclerosis.Journal of occupational and environmental medicine · 2014Pooled it
- Pooled it
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- Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?Molecular neurobiology · 2025Review
- Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications.Journal of neurology, neurosurgery, and psychiatry · 2025Article
- Comparison of Demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data.Journal of racial and ethnic health disparities · 2025Article
- Repeat expansion disorders.Practical neurology · 2025Review
- Rare Diseases, Spotlighting Amyotrophic Lateral Sclerosis, Huntington's Disease, and Myasthenia Gravis: Insights from Landscape Analysis of Current Research.Biochemistry · 2025Review
- Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.The Lancet. Neurology · 2025Review
- The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Cumulative incidence of motor and cognitive features in the amyotrophic lateral sclerosis-frontotemporal degeneration spectrum.Brain communications · 2025Article
- The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK.American journal of human genetics · 2024Article
- Article
- Study insights in the role of PGC-1α in neurological diseases: mechanisms and therapeutic potential.Frontiers in aging neuroscience · 2024Review
- Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.Translational neurodegeneration · 2023Review
- Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA.Nature communications · 2023Article
- Amyotrophic lateral sclerosis: translating genetic discoveries into therapies.Nature reviews. Genetics · 2023Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
46 authors.
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Abstract
A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n=1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n=434) and controls (n=856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.
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