ArticleArchives of neurology2012
Investigation of c9orf72 in 4 neurodegenerative disorders.
Article in Archives of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 3 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers: A Systematic Review and Meta-analysis.JAMA neurology · 2020Pooled it
- Atypical parkinsonism in C9orf72 expansions: a case report and systematic review of 45 cases from the literature.Journal of neurology · 2016Pooled it
- Pooled it
- Methodological insights and clinical outcomes in ALS and FTLD: lessons from the SPIN cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neurodegenerative disease in C9orf72 repeat expansion carriers: population risk and effect of UNC13A.Brain : a journal of neurology · 2025Article
- Protein Structure-based FUS Mutational Subtypes Are Associated With Protein Mislocalization in Amyotrophic Lateral Sclerosis Patients.Molecular neurobiology · 2025Article
- Next Generation Sequencing Analysis in Patients Affected by Parkinson's Disease and Correlation Between Genotype and Phenotype in Selected Clinical Cases.International journal of molecular sciences · 2025Article
- Distribution of theFrontiers in neurology · 2024Article
- Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, and Huntington's Diseases and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Review
- The genetic basis of multiple system atrophy.Journal of translational medicine · 2023Review
- Article
- Letter to the editor on a paper by Kaivola et al. (2020): carriership of two copies of C9orf72 hexanucleotide repeat intermediate-length alleles is not associated with amyotrophic lateral sclerosis or frontotemporal dementia.Acta neuropathologica communications · 2022Article
- Contribution of rare variant associations to neurodegenerative disease presentation.NPJ genomic medicine · 2021Article
- Article
- White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer's disease.Alzheimer's research & therapy · 2021Article
- Clinical Update on C9orf72: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and Beyond.Advances in experimental medicine and biology · 2021Article
- A Systematic Review of Genotype-Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS.Journal of personalized medicine · 2020Review
- C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition.Neurobiology of aging · 2019Article
- C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy.Acta neuropathologica · 2019Article
- Synaptic localization of C9orf72 regulates post-synaptic glutamate receptor 1 levels.Acta neuropathologica communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors at 11 institutions in 6 countries.
Funding
Abstract
OBJECTIVE To estimate the allele frequency of C9orf72 (G4C2) repeats in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and Parkinson disease (PD). DESIGN The number of repeats was estimated by a 2-step genotyping strategy. For expansion carriers, we sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2 haplotypes. SETTING Hospitals specializing in neurodegenerative disorders. SUBJECTS We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD with the LRRK2 G2019S mutation. MAIN OUTCOME MEASURE The expansion frequency. RESULTS Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3% of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD but not in controls or patients with AD. It was significantly associated with family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS vs FTLD) was not associated with MAPT, APOE, or variability in the repeat flanking regions. Two patients with PD were carriers of 39 and 32 repeats with questionable pathological significance, since the 39-repeat allele does not segregate with PD. No expansion or intermediate alleles (20-29 repeats) were found among the G2019S carriers and AD cases with TAR DNA-binding protein 43-positive inclusions. Surprisingly, the frequency of the 10-repeat allele was marginally increased in all 4 neurodegenerative diseases compared with controls, indicating the presence of an unknown risk variation in the C9orf72 locus. CONCLUSIONS The C9orf72 expansion is a common cause of ALS and FTLD, but not of AD or PD. Our study raises concern about a reliable cutoff for the pathological repeat number, which is important in the utility of genetic screening.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.