ReviewJournal of medical genetics2017
Intermediate C9orf72 alleles in neurological disorders: does size really matter?
Review in Journal of medical genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis 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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pooled it
- 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
- Parkinsonism in complex neurogenetic disorders: lessons from hereditary dementias, adult-onset ataxias and spastic paraplegias.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- No Association of Multiple Sclerosis withInternational journal of molecular sciences · 2023Article
- Young Onset Alzheimer's Disease Associated withGenes · 2023Article
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 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
- Expanding Clinical Spectrum ofNeurology. Genetics · 2022Review
- An exploratory pilot study on the involvement of APOE, HFE, C9ORF72 variants and comorbidities in neurocognitive and physical performance in a group of HIV-infected people.Metabolic brain disease · 2022Article
- Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions.Translational psychiatry · 2021Article
- Article
- Carriership of two copies of C9orf72 hexanucleotide repeat intermediate-length alleles is a risk factor for ALS in the Finnish population.Acta neuropathologica communications · 2020Article
- Review
- New Roles for Canonical Transcription Factors in Repeat Expansion Diseases.Trends in genetics : TIG · 2020Review
- C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition.Neurobiology of aging · 2019Article
- Links Between the C9orf72 Repeat Expansion and Psychiatric Symptoms.Current neurology and neuroscience reports · 2019Review
- Neurotheranostics as personalized medicines.Advanced drug delivery reviews · 2019Review
- An update on genetic frontotemporal dementia.Journal of neurology · 2019Review
- A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia.Progress in neuro-psychopharmacology & biological psychiatry · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C9orf72 repeat expansions is a major cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Sizes of <20 hexanucleotide repeats are observed in controls, while up to thousands associate with disease. Intermediate C9orf72 repeat lengths, however, remain uncertain. We systematically reviewed the role of intermediate C9orf72 alleles in C9orf72-related neurological disorders. We identified 49 studies with adequate available data on normal or intermediate C9orf72 repeat length, involving subjects with FTD, ALS, Parkinson's disease (PD), atypical parkinsonism, Alzheimer's disease (AD) and other aetiologies. We found that, overall, normal or intermediate C9orf72 repeat lengths are not associated with higher disease risk across these disorders, but intermediate allele sizes appear to associate more frequently with neuropsychiatric phenotypes. Intermediate sizes were detected in subjects with personal or family history of FTD and/or psychiatric illness, parkinsonism complicated by psychosis and rarely in psychiatric cohorts. Length of the hexanucleotide repeat may be influenced by ethnicity (with Asian controls displaying shorter normal repeat lengths compared with Caucasians) and underlying haplotype, with more patients and controls carrying the 'risk' haplotype rs3849942 displaying intermediate alleles. There is some evidence that intermediate alleles display increased methylation levels and affect normal transcriptional activity of the C9orf72 promoter, but the 'critical' repeat size required for initiation of neurodegeneration remains unknown and requires further study. In common neurological diseases, intermediate C9orf72 repeats do not influence disease risk but may associate with higher frequency of neuropsychiatric symptoms. This has important clinical relevance as intermediate carriers pose a challenge for genetic counselling.
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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.