Cited by 345Amyotrophic Lateral Sclerosis ResearchGenetic Neurodegenerative DiseasesAlzheimer's disease research and treatments

The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index.

Large C9orf72 Hexanucleotide Repeat Expansions Are Seen in Multiple Neurodegenerative Syndromes and Are More Frequent Than Expected in the UK Population

Open access

Beck, Jon, Poulter, Mark, Hensman, Davina, Rohrer, Jonathan D., Mahoney, Colin J., Adamson, Gary, Campbell, Tracy, Uphill, James, Borg, Aaron, Fratta, Pietro, Orrell, Richard W., Malaspina, Andrea, Rowe, James, Brown, Jeremy, Hodges, John, Sidle, Katie, Polke, James M., Houlden, Henry, Schott, Jonathan M., Fox, Nick C., Rossor, Martin N., Tabrizi, Sarah J., Isaacs, Adrian M., Hardy, John, Warren, Jason D., Collinge, John, Mead, Simon·2013·The American Journal of Human Genetics

DOI 10.1016/j.ajhg.2013.01.011PMC PMC3591848

Open this paper in CoChat — free account Open PDF

Abstract

Hexanucleotide repeat expansions in C9orf72 are a major cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Understanding the disease mechanisms and a method for clinical diagnostic genotyping have been hindered because of the difficulty in estimating the expansion size. We found 96 repeat-primed PCR expansions: 85/2,974 in six neurodegenerative diseases cohorts (FTLD, ALS, Alzheimer disease, sporadic Creutzfeldt-Jakob disease, Huntington disease-like syndrome, and other nonspecific neurodegenerative disease syndromes) and 11/7,579 (0.15%) in UK 1958 birth cohort (58BC) controls. With the use of a modified Southern blot method, the estimated expansion range (smear maxima) in cases was 800-4,400. Similarly, large expansions were detected in the population controls. Differences in expansion size and morphology were detected between DNA samples from tissue and cell lines. Of those in whom repeat-primed PCR detected expansions, 68/69 were confirmed by blotting, which was specific for greater than 275 repeats. We found that morphology in the expansion smear varied among different individuals and among different brain regions in the same individual. Expansion size correlated with age at clinical onset but did not differ between diagnostic groups. Evidence of instability of repeat size in control families, as well as neighboring SNP and microsatellite analyses, support multiple expansion events on the same haplotype background. Our method of estimating the size of large expansions has potential clinical utility. C9orf72-related disease might mimic several neurodegenerative disorders and, with potentially 90,000 carriers in the United Kingdom, is more common than previously realized.

Integrity signals

Registry

Crossref · 10.1016/j.ajhg.2013.01.011

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409
Self-citation
A high-resolution recombination map of the human genome
Kong, A., Gudbjartsson, D. F., Sainz, J., Jonsdottir, G. M., Gudjonsson, S. A., Richardsson, B., Sigurdardottir, S. L., Barnard, J., Hallbeck, B., Másson, G., et al. (2002) · Nature Genetics · doi:10.1038/ng917 · Cited by 1,750
Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study
Majounie, E., Renton, A. E., Mok, K., Dopper, E. G., Waite, A., Rollinson, S., Chiò, A., Restagno, G., Nicolaou, N., Simon-Sanchez, J., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70043-1 · Cited by 1,210
Self-citation
Expandable DNA repeats and human disease
Mirkin, S. M. (2007) · Nature · doi:10.1038/nature05977 · Cited by 934
A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study
Gijselinck, I., Langenhove, T. V., van der Zee, J., Sleegers, K., Philtjens, S., Kleinberger, G., Janssens, J., Bettens, K., Cauwenberghe, C. V., Pereson, S., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70261-7 · Cited by 655
The heritability and genetics of frontotemporal lobar degeneration
Rohrer, J. D., Guerreiro, R., Vandrovcova, J., Uphill, J., Reiman, D., Beck, J., Isaacs, A. M., Authier, A., Ferrari, R., Fox, N. C., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bf997a · Cited by 536
Self-citation
Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations
Snowden, J. S., Rollinson, S., Thompson, J. C., Harris, J. M., Stopford, C. L., Richardson, A. M. T., Jones, M., Gerhard, A., Davidson, Y. S., Robinson, A., et al. (2012) · Brain · doi:10.1093/brain/awr355 · Cited by 523
Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features
Mahoney, C., Beck, J. A., Rohrer, J. D., Lashley, T., Mok, K. Y., Shakespeare, T. J., Yeatman, T., Warrington, E. K., Schott, J. M., Fox, N. C., et al. (2012) · Brain · doi:10.1093/brain/awr361 · Cited by 452
Self-citation
Sticky DNA
Sakamoto, N., Chastain, P. D., Parniewski, P., Ohshima, K., Pandolfo, M., Griffith, J. D., & Wells, R. D. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80474-8 · Cited by 313

Show all 25 references

Research works printed but not linked: 1

Smith, 2012, The C9ORF72 expansion mutation has a single European founder that arose from a background haplotype associated with repeat instability, Dement. Geriatr. Cogn. Disord., 33, 87

Sorted by citations

Items 101–200 of 345

Improved PCR based methods for detecting C9orf72 hexanucleotide repeat expansions
Cleary, E. M., Pal, S., Azam, T., Moore, D., Swingler, R. J., Gorrie, G., Stephenson, L. J., Colville, S., Chandran, S., Porteous, M. E., et al. (2016) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2016.06.001 · Cited by 46
Gene expression profiles and protein-protein interaction networks in amyotrophic lateral sclerosis patients with C9orf72 mutation
Kotni, M. K., Zhao, M., & Wei, D. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0531-y · Cited by 45
Modelling C9orf72 dipeptide repeat proteins of a physiologically relevant size
Callister, J. B., Ryan, S., Sim, J. A., Rollinson, S. J., & Pickering-Brown, S. M. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw327 · Cited by 41
Neuroinflammation in Amyotrophic Lateral Sclerosis: Role of Redox (dys)Regulation
D’Ambrosi, N., Cozzolino, M., & Carrı̀, M. T. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7271 · Cited by 44
Pathogenic determinants and mechanisms of ALS/FTD linked to hexanucleotide repeat expansions in the C9orf72 gene
Wen, X., Westergard, T., Pasinelli, P., & Trotti, D. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.09.007 · Cited by 45
The Genetics of C9orf72 ExpansionsPreprint
Gijselinck, I., Cruts, M., & Broeckhoven, C. V. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026757 · Cited by 43
Searching for Grendel: origin and global spread of the C9ORF72 repeat expansion
Pliner, H. A., Mann, D. M. A., & Traynor, B. J. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1250-x · Cited by 42
A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia
Lashley, T., Rohrer, J. D., Mahoney, C., Gordón, E., Beck, J. A., Mead, S., Warren, J. D., Rossor, M. N., & Révész, T. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12100 · Cited by 42
Self-citation
Expanding Clinical Spectrum of C9ORF72 -Related Disorders and Promising Therapeutic Strategies
Breevoort, S. R., Gibson, S. B., Figueroa, K. P., Bromberg, M. B., & Pulst, S. M. (2022) · Neurology Genetics · doi:10.1212/nxg.0000000000000670 · Cited by 42
The role of C9orf72 in neurodegenerative disorders: a systematic review, an updated meta-analysis, and the creation of an online database
Marogianni, C., Rikos, D., Provatas, A., Dadouli, K., Ntellas, P., Tsitsi, P., Patrinos, G. P., Dardiotis, E., Hadjigeorgiou, G. M., & Xiromerisiou, G. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.04.012 · Cited by 41
Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers
Cammack, A. J., Atassi, N., Hyman, T. S., van den Berg, L. H., Harms, M. B., Baloh, R. H., Brown, R. H., van Es, M. A., Veldink, J. H., de Vries, B. S., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008359 · Cited by 46
Pathogenic Mechanisms and Therapy Development for C9orf72 Amyotrophic Lateral Sclerosis/Frontotemporal Dementia
Jiang, J., & Ravits, J. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00797-2 · Cited by 44
A 30-unit hexanucleotide repeat expansion in C9orf72 induces pathological lesions with dipeptide-repeat proteins and RNA foci, but not TDP-43 inclusions and clinical disease
Gami‐Patel, P., Murray, C. E., Schottlaender, L., Bettencourt, C., Pablo‐Fernández, E. D., Mudanohwo, E. E., Mizielinska, S., Polke, J. M., Holton, J. L., Isaacs, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1473-5 · Cited by 38
Self-citation
C9orf72 expansion as a possible genetic cause of Huntington disease phenocopy syndrome
Kostić, V. S., Dobričić, V., Stanković, I., Ralić, V., & Stefanova, E. (2014) · Journal of Neurology · doi:10.1007/s00415-014-7430-8 · Cited by 37
The behavioural variant frontotemporal dementia phenocopy syndrome is a distinct entity - evidence from a longitudinal study
Devenney, E., Swinn, T., Mioshi, E., Hornberger, M., Dawson, K. E., Mead, S., Rowe, J. B., & Hodges, J. R. (2018) · BMC Neurology · doi:10.1186/s12883-018-1060-1 · Cited by 37
Self-citation
Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges
Zhu, L., Li, S., Li, X., & Yin, P. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00377-7 · Cited by 41
Unstable repeat expansions in neurodegenerative diseases: nucleocytoplasmic transport emerges on the scene
Loureiro, J. R., Oliveira, C. L., & Silveira, I. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.12.007 · Cited by 38
Multiple variants in families with amyotrophic lateral sclerosis and frontotemporal dementia related to C9orf72 repeat expansion: further observations on their oligogenic nature
Giannoccaro, M. P., Bartoletti‐Stella, A., Piras, S., Pession, A., Massis, P. D., Oppi, F., Maserati, M. S., Pasini, E., Baiardi, S., Avoni, P., et al. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8540-x · Cited by 37
Expanding the Spectrum of Movement Disorders Associated With C9orf72 Hexanucleotide Expansions
Estevez‐Fraga, C., Magrinelli, F., Moss, D. J. H., Mulroy, E., Lazzaro, G. D., Latorre, A., Mackenzie, M., Houlden, H., Tabrizi, S. J., & Bhatia, K. P. (2021) · Neurology Genetics · doi:10.1212/nxg.0000000000000575 · Cited by 36
Self-citation
Where and Why Modeling Amyotrophic Lateral Sclerosis
Liguori, F., Amadio, S., & Volonté, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083977 · Cited by 36
Reduced penetrance of gene variants causing amyotrophic lateral sclerosis
Douglas, A. G. L., & Baralle, D. (2023) · Journal of Medical Genetics · doi:10.1136/jmg-2023-109580 · Cited by 35
C9orf72 repeat expansions are restricted to the ALS-FTD spectrum
Ticozzi, N., Tiloca, C., Calini, D., Gagliardi, S., Altieri, A., Colombrita, C., Cereda, C., Ratti, A., Pezzoli, G., Borroni, B., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.037 · Cited by 33
Analysis of the hexanucleotide repeat expansion and founder haplotype at C9ORF72 in an Irish psychosis case-control sample
Fahey, C., Byrne, S., McLaughlin, R. L., Kenna, K. P., Shatunov, A., Donohoe, G. J., Gill, M., Al‐Chalabi, A., Bradley, D. G., Hardiman, O. M., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.003 · Cited by 35
Links Between the C9orf72 Repeat Expansion and Psychiatric Symptoms
Silverman, H. E., Goldman, J. S., & Huey, E. D. (2019) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-019-1017-9 · Cited by 36
Fly for ALS: Drosophila modeling on the route to amyotrophic lateral sclerosis modifiers
Liguori, F., Amadio, S., & Volonté, C. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03905-8 · Cited by 35
Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing
Jagtap, Y. A., Kumar, P., Kinger, S., Dubey, A. R., Choudhary, A., Gutti, R. K., Singh, S., Jha, H. C., Poluri, K. M., & Mishra, A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1146564 · Cited by 36
Genetic modifiers of repeat expansion disorders
Rajagopal, S., Donaldson, J., Flower, M. D., Moss, D. J. H., & Tabrizi, S. J. (2023) · Emerging Topics in Life Sciences · doi:10.1042/etls20230015 · Cited by 32
Self-citation
C9ORF72 hexanucleotide repeat expansions are a frequent cause of Huntington disease phenocopies in the Greek population
Koutsis, G., Karadima, G., Kartanou, C., Kladi, A., & Πάνας, Μ. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.020 · Cited by 33
C9ORF72 Mutations in Neurodegenerative Diseases
Liu, Y., Yu, J., Zong, Y., Zhou, J., & Tan, L. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8528-1 · Cited by 36
Drosha Inclusions Are New Components of Dipeptide-Repeat Protein Aggregates in FTLD-TDP and ALSC9orf72Expansion Cases
Porta, S., Kwong, L. K., Trojanowski, J. Q., & Lee, V. M. ‐. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000182 · Cited by 34
Co-expression of C9orf72 related dipeptide-repeats over 1000 repeat units reveals age- and combination-specific phenotypic profiles in Drosophila
West, R. J. H., Sharpe, J. L., Voelzmann, A., Munro, A. L., Hahn, I., Baines, R., & Pickering-Brown, S. M. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01028-y · Cited by 35
Amyotrophic lateral sclerosis
Sreedharan, J., Blakeney, I., & Brown, R. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813866-3.00020-5 · Cited by 32
Calculating variant penetrance from family history of disease and average family size in population-scale data
Spargo, T. P., Opie-Martin, S., Bowles, H., Lewis, C. M., Iacoangeli, A., & Al‐Chalabi, A. (2022) · Genome Medicine · doi:10.1186/s13073-022-01142-7 · Cited by 29
Assessment of risk of ALS conferred by the GGGGCC hexanucleotide repeat expansion in C9orf72 among first-degree relatives of patients with ALS carrying the repeat expansion
van Wijk, I. F., van Eijk, R. P. A., van Boxmeer, L., Westeneng, H., van Es, M. A., van Rheenen, W., van den Berg, L. H., Eijkemans, M. J. C., & Veldink, J. H. (2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2272187 · Cited by 29
A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
Cortese, A., Beecroft, S. J., Facchini, S., Curró, R., Cabrera‐Serrano, M., Stevanovski, I., Chintalaphani, S. R., Gamaarachchi, H., Weisburd, B., Folland, C. L., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49950-2 · Cited by 30
Self-citation
C9orf72 Intermediate Alleles in Patients with Amyotrophic Lateral Sclerosis, Systemic Lupus Erythematosus, and Rheumatoid Arthritis
Fredi, M., Cavazzana, I., Biasiotto, G., Filosto, M., Padovani, A., Monti, E., Tincani, A., Franceschini, F., & Zanella, I. (2019) · NeuroMolecular Medicine · doi:10.1007/s12017-019-08528-8 · Cited by 31
Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer’s Disease
Jordan, K. L., Koss, D. J., Outeiro, T. F., & Giorgini, F. (2022) · Biomedicines · doi:10.3390/biomedicines10051141 · Cited by 32
Amyotrophic Lateral Sclerosis Genetic Studies
He, J., Mangelsdorf, M., Fan, D., Bartlett, P. F., & Brown, M. A. (2014) · The Neuroscientist · doi:10.1177/1073858414555404 · Cited by 30
GIPC1 CGG Repeat Expansion Is Associated with Movement Disorders
Fan, Y., Shen, S., Yang, J., Yao, D., Li, M., Mao, C., Wang, Y., Hao, X., Ma, D., Li, J., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26325 · Cited by 29
Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72 -associated frontotemporal dementia and amyotrophic lateral sclerosis
Wilson, K. M., Katona, E., Glaria, I., Carcolé, M., Swift, I. J., Sogorb‐Esteve, A., Heller, C., Bouzigues, A., Heslegrave, A., Keshavan, A., et al. (2022) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2021-328710 · Cited by 31
Self-citation
Absence of C9ORF72 expanded or intermediate repeats in autopsy‐confirmed Parkinson's disease
Nuytemans, K., Inchausti, V., Beecham, G. W., Wang, L., Dickson, D. W., Trojanowski, J. Q., Lee, V. M. ‐., Mash, D. C., Frosch, M. P., Foroud, T., et al. (2014) · Movement Disorders · doi:10.1002/mds.25838 · Cited by 28
Large-scale screening in sporadic amyotrophic lateral sclerosis identifies genetic modifiers in C9orf72 repeat carriers
Dekker, A. M., Seelen, M., van Doormaal, P. T. C., van Rheenen, W., Bothof, R., van Riessen, T., Brands, W. J., van der Kooi, A. J., de Visser, M., Voermans, N. C., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.12.012 · Cited by 28
Structural insight into C9orf72 hexanucleotide repeat expansions: Towards new therapeutic targets in FTD-ALS
Kumar, V., Kashav, T., Islam, A., Ahmad, F., & Hassan, M. I. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.08.008 · Cited by 28
NEAT1 lncRNA and amyotrophic lateral sclerosis
Nishimoto, Y., Nakagawa, S., & Okano, H. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105175 · Cited by 28
Motor, cognitive and behavioural profiles of C9orf72 expansion-related amyotrophic lateral sclerosis
Colombo, E., Poletti, B., Maranzano, A., Peverelli, S., Solca, F., Colombrita, C., Torre, S., Tiloca, C., Verde, F., Bonetti, R., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11433-z · Cited by 27
Genetic variation associated with the occurrence and progression of neurological disorders
Little, J., Barakat, C., Martino, R., Pringsheim, T. M., Tremlett, H. L., McKay, K. A., Lieshout, P. H. H. M. V., Walsh, S. J., Gomes, J., & Krewski, D. R. (2016) · NeuroToxicology · doi:10.1016/j.neuro.2016.09.018 · Cited by 28
Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease
Wang, G., Zhang, D., Jiang, H., Fan, Y., Ma, L., Shen, Z., Bi, R., Xu, M., Tan, L., Shan, B., et al. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.03.026 · Cited by 27
A mouse model with widespread expression of the C9orf72-linked glycine–arginine dipeptide displays non-lethal ALS/FTD-like phenotypes
Verdone, B. M., Cicardi, M. E., Wen, X., Sriramoji, S., Russell, K. A., Markandaiah, S. S., Jensen, B. K., Krishnamurthy, K., Haeusler, A. R., Pasinelli, P., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-09593-z · Cited by 23
C9orf72-related disorders: expanding the clinical and genetic spectrum of neurodegenerative diseases
de Souza, P. V. S., Pinto, W. B. V. D. R., & Oliveira, A. S. B. (2015) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20140229 · Cited by 26
A systematic review of neuroimaging studies
de Godoy, L., Prado, R., Bicalho, I. C. S., Magalhães, D., Caramelli, P., Teixeira, A. L., & de Souza, L. C. (2015) · Cited by 25
Novel Imaging Biomarkers for Huntington’s Disease and Other Hereditary Choreas
Fazio, P., Paucar, M., Svenningsson, P., & Varrone, A. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0890-y · Cited by 24
C9orf72 repeat expansions that cause frontotemporal dementia are detectable among patients with psychosis
Watson, A. M. M., Pribadi, M., Chowdari, K. V., Clifton, S., Wood, J. A., Miller, B. L., Coppola, G., & Nimgaonkar, V. L. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.12.007 · Cited by 25
Large scale in silico characterization of repeat expansion variation in human genomes
Fazal, S., Danzi, M. C., Cintra, V. P., Bis‐Brewer, D. M., Dolzhenko, E., Eberle, M. A., & Zuchner, S. L. (2020) · Scientific Data · doi:10.1038/s41597-020-00633-9 · Cited by 25
The clinical and pathological phenotypes of frontotemporal dementia with C9ORF72 mutations
Liu, Y., Yu, J., Sun, F.-R., Ou, J.-R., Qu, S.-B., & Tan, L. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.09.013 · Cited by 27
Singling out motor neurons in the age of single-cell transcriptomics
Blum, J. A., & Gitler, A. D. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.03.016 · Cited by 22
A small deletion in C9orf72 hides a proportion of expansion carriers in FTLD
Rollinson, S. J., Callister, J. B., Young, K., Ryan, S., Druyeh, R., Rohrer, J. D., Snowden, J. S., Richardson, A. M. T., Jones, M., Harris, J., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.12.009 · Cited by 24
Self-citation
Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat
Jones, A. R., Woollacott, I., Shatunov, A., Cooper‐Knock, J., Buchman, V. L., Sproviero, W., Smith, B. N., Scott, K. M., Balendra, R., Abel, O., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.003 · Cited by 26
A blood–brain penetrant RNA-targeted small molecule triggers elimination of r(G 4 C 2 ) exp in c9ALS/FTD via the nuclear RNA exosome
Bush, J. A., Meyer, S. M., Fuerst, R., Tong, Y., Li, Y., Benhamou, R. I., Aikawa, H., Zanon, P. R. A., Gibaut, Q. M. R., Angelbello, A. J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210532119 · Cited by 23
C9orf72 Repeat Expansions in Rapid Eye Movement Sleep Behaviour Disorder
Daoud, H., Postuma, R. B., Bourassa, C. V., Rochefort, D. L., Gauthier, M. T., Montplaisir, J. Y., Gagnon, J., Arnulf, I., Dauvilliers, Y. A., Charley, C. M., et al. (2014) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2014.39 · Cited by 23
C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
Zampatti, S., Peconi, C., Campopiano, R., Gambardella, S., Caltagirone, C., & Giardina, E. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.907122 · Cited by 22
Carriership of two copies of C9orf72 hexanucleotide repeat intermediate-length alleles is a risk factor for ALS in the Finnish population
Kaivola, K., Salmi, S. J., Jansson, L., Launes, J., Hokkanen, L., Niemi, A., Majamaa, K., Lahti, J. M. T., Eriksson, J. G., Strandberg, T. E., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01059-5 · Cited by 21
Frontotemporal Dementia and Glucose Metabolism
Garrett, L. R., & Niccoli, T. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.812222 · Cited by 20
C9orf72-associated SMCR8 protein binds in the ubiquitin pathway and with proteins linked with neurological disease
Goodier, J. L., Soares, A. O., Pereira, G., Devine, L. R., Sánchez, L., Cole, R. N., & Garcia-Perez, J. L. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00982-x · Cited by 21
Proteostasis impairment and ALS
Lambert-Smith, I. A., Saunders, D. N., & Yerbury, J. J. (2022) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2022.06.001 · Cited by 19
The evolution of comprehensive genetic analysis in neurology: Implications for precision medicine
Papadopoulou, E., Pepe, G., Konitsiotis, S., Chondrogiorgi, M., Grigoriadis, N., Kimiskidis, V. Κ., Tsivgoulis, G. K., Mitsikostas, D. D., Chroni, E., Domouzoglou, E. M., et al. (2023) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2023.120609 · Cited by 22
C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?
Sellier, C., Corcia, P., Vourc’h, P., & Dupuis, L. (2024) · Revue Neurologique · doi:10.1016/j.neurol.2024.03.008 · Cited by 24
The C9orf72 hexanucleotide repeat expansion presents a challenge for testing laboratories and genetic counseling
Crook, A., McEwen, A., Fifita, J. A., Zhang, K., Kwok, J. B., Halliday, G. M., Blair, I. P., & Rowe, D. B. (2019) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2019.1588904 · Cited by 20
C9orf72 repeat expansions in South Africans with amyotrophic lateral sclerosis
Nel, M., Agenbag, G., Henning, F., Cross, H., Esterhuizen, A. I., & Heckmann, J. M. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.04.026 · Cited by 20
Non-coding RNA in C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction
Douglas, A. G. L. (2018) · Non-coding RNA Research · doi:10.1016/j.ncrna.2018.09.001 · Cited by 20
C9ORF72‐ALS: P62‐ and ubiquitin‐aggregation pathology in skeletal muscle
Türk, M., Haaker, G., Winter, L., Just, W., Nickel, F. T., Linker, R. A., Chevessier, F., & Schröder, R. (2014) · Muscle & Nerve · doi:10.1002/mus.24283 · Cited by 18
C9orf72 and the Care of the Patient With ALS or FTD
Roggenbuck, J. (2020) · Neurology Genetics · doi:10.1212/nxg.0000000000000542 · Cited by 18
Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions
Reus, L. M., Jansen, I. E., Mol, M. O., van Ruissen, F., van Rooij, J., van Schoor, N. M., Tesi, N., Reinders, M. J. T., Huisman, M. A., Holstege, H. H., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01577-3 · Cited by 18
Epidemiology and molecular mechanism of frontotemporal lobar degeneration/amyotrophic lateral sclerosis with repeat expansion mutation inC9orf72
Ishiura, H., & Tsuji, S. (2015) · Journal of Neurogenetics · doi:10.3109/01677063.2015.1085980 · Cited by 19
Slowly progressive behavioral frontotemporal dementia with C9orf72 mutation. Case report and review of the literature
Velasco, S. L., García‐Redondo, A., Martín, A. H.-S., Puertas‐Martín, V., González‐Sánchez, M., Pérez-Martínez, D. A., & Villarejo‐Galende, A. (2018) · Neurocase · doi:10.1080/13554794.2018.1428353 · Cited by 18
Familial benign frontotemporal deterioration with C9ORF72 hexanucleotide expansion
Gómez‐Tortosa, E., Serrano, S., de Toledo, M., Pérez‐Pérez, J., & Sainz, M. J. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.09.013 · Cited by 18
The Association between C9orf72 Repeats and Risk of Alzheimer’s Disease and Amyotrophic Lateral Sclerosis: A Meta-Analysis
Li, S., Sun, Q., Zhang, Y., Xu, Q., Guo, J., Yan, X., & Tang, B. (2016) · Parkinson s Disease · doi:10.1155/2016/5731734 · Cited by 18
C9orf72; abnormal RNA expression is the key
Heutink, P., Jansen, I. E., & Lynes, E. M. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.05.020 · Cited by 17
C9ORF72 and the FTD-ALS spectrum: a systematic review of neuroimaging studies
Prado, L. D. G. R., Bicalho, I. C. S., Magalhães, D., Caramelli, P., Teixeira, A. L., & de Souza, L. C. (2015) · Dementia & Neuropsychologia · doi:10.1590/1980-57642015dn94000413 · Cited by 17
High frequency of C9orf72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis patients from two founder populations sharing the same risk haplotype
Goldstein, O., Gana‐Weisz, M., Nefussy, B., Vainer, B., Nayshool, O., Bar‐Shira, A., Traynor, B. J., Drory, V. E., & Orr‐Urtreger, A. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.12.015 · Cited by 17
Comprehensive genotyping of the C9orf72 hexanucleotide repeat region in 2095 ALS samples from the NINDS collection using a two-mode, long-read PCR assay
Bram, E. E., Javanmardi, K., Nicholson, K., Culp, K., Thibert, J. R., Kemppainen, J., Le, V. V., Schlageter, A. M., Hadd, A. G., & Latham, G. J. (2018) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2018.1522353 · Cited by 17
C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition
Kaivola, K., Kiviharju, A., Jansson, L., Rantalainen, V. J., Eriksson, J. G., Strandberg, T. E., Laaksovirta, H., Renton, A. E., Traynor, B. J., Myllykangas, L., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.026 · Cited by 17
Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis
Patel, A. N., & Sampson, J. B. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0582-9 · Cited by 17
Frontotemporal dementia with a C9ORF72 expansion in a Swedish family: clinical and neuropathological characteristics.
Waldö, M. L., Gustafson, L., Nilsson, K. H., Traynor, B. J., Renton, A. E., Englund, E. M., & Passant, U. (2013) · Europe PMC (PubMed Central) · Cited by 17
C9ORF72 repeat expansions in Chinese patients with Parkinson’s disease and multiple system atrophy
Chen, X., Chen, Y., Wei, Q., Ou, R., Cao, B., Zhao, B., & Shang, H. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1598-2 · Cited by 17
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability
Jadhav, B., Garg, P., van Vugt, J. J. F. A., Ibáñez, K., Gagliardi, D., Lee, W., Shadrina, M., Mokveld, T., Dolzhenko, E., Martin-Trujillo, A., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01917-1 · Cited by 22
Self-citation
C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Cruts, M., Engelborghs, S., van der Zee, J., & Broeckhoven, C. V. (2015) · VUBIR (Vrije Universiteit Brussel) · Cited by 16
Clinical and biological phenotypes of frontotemporal dementia: Perspectives for disease modifying therapies
Gazzina, S., Manes, M. A., Padovani, A., & Borroni, B. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.05.056 · Cited by 21
Differences in Motor Features of C9orf72 , MAPT , or GRN Variant Carriers With Familial Frontotemporal Lobar Degeneration
Tipton, P. W., Deutschlaender, A., Savica, R., Heckman, M. G., Brushaber, D. E., Dickerson, B. C., Gavrilova, R. H., Geschwind, D. H., Ghoshal, N., Graff‐Radford, J., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000200860 · Cited by 18
Interface of G-quadruplex with both stabilizing and destabilizing ligands for targeting various diseases
Chaudhary, S., Kumar, M., & Kaushik, M. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.07.248 · Cited by 15
A familial frontotemporal dementia associated with C9orf72 repeat expansion and dysplastic gangliocytoma
Ferrari, R., Kero, M., Mok, K. Y., Paetau, A. E., Tienari, P. J., Tynninen, O., Hardy, J., Momeni, P., Verkkoniemi‐Ahola, A., & Myllykangas, L. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.08.021 · Cited by 15
Self-citation
Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies
Kun‐Rodrigues, C., Ross, O. A., Orme, T., Shepherd, C. E., Parkkinen, L., Darwent, L., Hernandez, D. G., Ansorge, O., Clark, L. N., Honig, L. S., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.023 · Cited by 15
Neurodegenerative disease in C9orf72 repeat expansion carriers: population risk and effect of UNC13A
Gao, J., Douglas, A. G. L., Chalitsios, C. V., Scaber, J., Talbot, K., Turner, M. R., & Thompson, A. G. (2025) · Brain · doi:10.1093/brain/awaf269 · Cited by 14
Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion
Udine, E., Finch, N. A., DeJesus‐Hernandez, M., Jackson, J. L., Baker, M., Saravanaperumal, S. A., Wieben, E. D., Ebbert, M., Shah, J., Petrucelli, L., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00790-0 · Cited by 14
Correlation between C9ORF72 mutation and neurodegenerative diseases: A comprehensive review of the literature
Xu, X., Su, Y., Zou, Z., Zhou, Y., & Yan, J. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.53550 · Cited by 15
C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age
Zanella, I., Zacchi, E., Piva, S., Filosto, M., Beligni, G., Alaverdian, D. A., Amitrano, S., Fava, F., Baldassarri, M., Frullanti, E., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136991 · Cited by 14
(C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6
Lat, P. K., & Sen, D. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198418 · Cited by 12
Analysis of the GGGGCC Repeat Expansions of the C9orf72 Gene in SCA3/MJD Patients from China
Wang, C., Zhao, C. N., Yang, F., Jiao, B., Peng, H., Shi, Y., Wang, Y., Huang, F., Wang, J., Shen, L. H., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130336 · Cited by 13
p62/SQSTM1 analysis in frontotemporal lobar degeneration
Miller, L., Rollinson, S. J., Callister, J. B., Young, K., Harris, J., Gerhard, A., Neary, D., Richardson, A. M. T., Snowden, J. S., Mann, D. M. A., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.035 · Cited by 13
Genetik der amyotrophen Lateralsklerose
Hübers, A., Weishaupt, J. H., & Ludolph, A. C. (2013) · Der Nervenarzt · doi:10.1007/s00115-013-3898-1 · Cited by 12
Pathological assessments for the presence of hexanucleotide repeat expansions in C9ORF72 in Alzheimer’s disease
Davidson, Y. S., Robinson, A., Snowden, J. S., & Mann, D. M. A. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-50 · Cited by 11

Authors: Beck, J., Poulter, M., Hensman, D., Rohrer, J. D., Mahoney, C. J., Adamson, G., Campbell, T., Uphill, J., Borg, A., Fratta, P., Orrell, R. W., Malaspina, A., Rowe, J., Brown, J., Hodges, J., Sidle, K., Polke, J. M., Houlden, H., Schott, J. M., Fox, N. C., Rossor, M. N., Tabrizi, S. J., Isaacs, A. M., Hardy, J., Warren, J. D., Collinge, J., & Mead, S.
Affiliations: MRC Prion Unit (GB)
UCL Queen Square Institute of Neurology (GB)
National Hospital for Neurology and Neurosurgery (GB)
Queen Mary University of London (GB)
University of Cambridge (GB)
Corresponding author: Mead, Simon
ORCID: Rohrer, Jonathan D.
Mahoney, Colin J.
Campbell, Tracy
Borg, Aaron
Fratta, Pietro
Malaspina, Andrea
Rowe, James
Brown, Jeremy
Hodges, John
Polke, James M.
Houlden, Henry
Schott, Jonathan M.
Fox, Nick C.
Rossor, Martin N.
Tabrizi, Sarah J.
Isaacs, Adrian M.
Hardy, John
Warren, Jason D.
Collinge, John
Mead, Simon
Venue: The American Journal of Human Genetics
Publisher: Elsevier BV
Published: 2013-03
Volume: 92
Issue: 3
Pages: 345-353
ISSN: 0002-9297 (ISSN-L)
DOI: 10.1016/j.ajhg.2013.01.011
PMC: PMC3591848
OpenAlex: W2026340703
Cited by: 345
References: 25
Citations by year: 2026: 4 · 2025: 6 · 2024: 24 · 2023: 24 · 2022: 31 · 2021: 21 · 2020: 20 · 2019: 21 · 2018: 27 · 2017: 21 · 2016: 24 · 2015: 44 · 2014: 41 · 2013: 35
FWCI: 30.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 193 d)
Locations: The American Journal of Human Genetics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Wellcome Trust (068545/Z/02), 088324, 091673/Z/10/Z, 068545)
National Institute for Health and Care Research (NF-SI-0512-10033, ACF-2009-18-016, NF-SI-0508-10123)
Motor Neurone Disease Association (Orrell/Apr11/6075)
Medical Research Council (MR/J004758/1, MR/J003832/1)
Topics: Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: C9orf72, hexanucleotide repeat expansion, repeat-primed PCR, Southern blot, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, Alzheimer's disease, Creutzfeldt-Jakob disease, repeat instability, haplotypes, age of onset, 1958 British birth cohort
MeSH terms: C9orf72 Protein, Amyotrophic Lateral Sclerosis, Brain, DNA, United Kingdom, Haplotypes, Humans, Nerve Degeneration, Proteins, Cohort Studies, Microsatellite Repeats, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, DNA Repeat Expansion, Frontotemporal Lobar Degeneration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Large C9orf72 Hexanucleotide Repeat Expansions Are Seen in Multiple Neurodegenerative Syndromes and Are More Frequent Than Expected in the UK Population

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks