C9orf72 Hexanucleotide Repeat Expansions in Clinical Alzheimer Disease
Open accessAbstract
IMPORTANCE: Hexanucleotide repeat expansions in the chromosome 9 open reading frame 72 (C9orf72) gene underlie a significant fraction of frontotemporal dementia and amyotrophic lateral sclerosis. OBJECTIVE: To investigate the frequency of C9orf72 repeat expansions in clinically diagnosed late-onset Alzheimer disease (AD). DESIGN, SETTING, AND PATIENTS: This case-control study genotyped the C9orf72 repeat expansion in 872 unrelated familial AD cases and 888 control subjects recruited as part of the National Institute on Aging Late-Onset Alzheimer Disease Family Study cohort, a multisite collaboration studying 1000 families with 2 or more individuals clinically diagnosed as having late-onset AD. MAIN OUTCOMES AND MEASURES: We determined the presence or absence of the C9orf72 repeat expansion by repeat-primed polymerase chain reaction, the length of the longest nonexpanded allele, segregation of the genotype with disease, and clinical features of repeat expansion carriers. RESULTS Three families showed large C9orf72 hexanucleotide repeat expansions. Two additional families carried more than 30 repeats. Segregation with disease could be demonstrated in 3 families. One affected expansion carrier had neuropathology compatible with AD. In the National Institute on Aging Late-Onset Alzheimer Disease Family Study series, the C9orf72 repeat expansions constituted the second most common pathogenic mutation, just behind the PSEN1 A79V mutation, highlighting the heterogeneity of clinical presentations associated with repeat expansions. CONCLUSIONS AND RELEVANCE: C9orf72 repeat expansions explain a small proportion of patients with a clinical presentation indistinguishable from AD, and they highlight the necessity of screening frontotemporal dementia genes in clinical AD cases with strong family history.
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C9orf72 expansion mutations are associated with ALS/FTLD and also with symptoms reminiscent of Parkinson disease, Alzheimer disease, Huntington disease, and corticobasal syndrome.
“For instance, C9orf72 expansion mutations are associated not only with ALS/FTLD, but also with symptoms reminiscent of Parkinson disease, Alzheimer disease, Huntington disease, and corticobasal syndrome, reinforcing the imperfect connection between clinical and molecular phenotypes and emphasizing the need for molecular diagnostics [155–164].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [158]
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McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
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 · see citing works
Self-citationGoate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · see citing works
Self-citationA 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 · see citing works
Alzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424 · see citing works
Self-citationThe Lewy body variant of Alzheimer's disease: A clinical and pathologic entity
Hansen, L., Salmon, D., Galasko, D., Masliah, E., Katzman, R., DeTeresa, R., Thal, L., Pay, M. M., Hofstetter, R., Klauber, M., et al. (1990) · Neurology · doi:10.1212/wnl.40.1.1 · Cited by 1,068 · see citing works
Berg, L., McKeel, D. W., Miller, J. P., Storandt, M., Rubin, E. H., Morris, J. C., Baty, J., Coats, M., Norton, J., Goate, A. M., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.326 · Cited by 657 · see citing works
Self-citationBoeve, B. F., Boylan, K., Graff‐Radford, N. R., DeJesus‐Hernandez, M., Knopman, D. S., Pedraza, O., Vemuri, P., Jones, D. T., Lowe, V. J., Murray, M. E., et al. (2012) · Brain · doi:10.1093/brain/aws004 · Cited by 344 · see citing works
Self-citationCruchaga, C., Chakraverty, S., Mayo, K., Vallania, F. L. M., Mitra, R. D., Faber, K., Williamson, J., Bird, T., Diaz-Arrastia, R., Foroud, T. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031039 · Cited by 320 · see citing works
Self-citationMurray, M. E., DeJesus‐Hernandez, M., Rutherford, N. J., Baker, M. C., Duara, R., Graff‐Radford, N. R., Wszołek, Z. K., Ferman, T. J., Josephs, K. A., Boylan, K., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0907-y · Cited by 295 · see citing works
Self-citationWijsman, E. M., Pankratz, N., Choi, Y., Rothstein, J. H., Faber, K. M., Cheng, R., Lee, J. H., Bird, T. D., Bennett, D. A., Diaz-Arrastia, R. R., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001308 · Cited by 223 · see citing works
Self-citationThe Lewy-Body Variant of Alzheimer's Disease
Förstl, H., Burns, A. S., Luthert, P. J., Cairns, N. J., & Levy, R. (1993) · The British Journal of Psychiatry · doi:10.1192/bjp.162.3.385 · Cited by 221 · see citing works
Self-citationRademakers, R., Baker, M. C., Gass, J. M., Adamson, J. L., Huey, E. D., Momeni, P., Spina, S., Coppola, G., Karydas, A. M., Stewart, H. G., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70221-1 · Cited by 211 · see citing works
Self-citationScreening for PS1 mutations in a referral-based series of AD cases
Rogaeva, E. A., Fafel, K. C., Song, Y., Medeiros, H., Sato, C., Liang, Y., Richard, E., Rogaev, E. I., Frommelt, P., Sadovnick, A. D., et al. (2001) · Neurology · doi:10.1212/wnl.57.4.621 · Cited by 203 · see citing works
Self-citationAutosomal dominant dementia with widespread neurofibrillary tangles
Reed, L. A., Schelper, R. L., Solodkin, A., Hoesen, G. W. V., Hoesen, G. W. V., Solodkin, A., Morris, J. C., Trojanowski, J. Q., Grabowski, T. J., Talbot, C. J., et al. (1997) · Annals of Neurology · doi:10.1002/ana.410420406 · Cited by 181 · see citing works
Self-citationLudolph, A. C., Kassubek, J., Landwehrmeyer, G. B., Mandelkow, E., Mandelkow, E., Burn, D. J., Caparros-Lefebvre, D., Frey, K. A., de Yébenes, J. G., Gasser, T., et al. (2009) · European Journal of Neurology · doi:10.1111/j.1468-1331.2008.02513.x · Cited by 170 · see citing works
Repeat Expansion inC9ORF72in Alzheimer's Disease
Majounie, E., Abramzon, Y. A., Renton, A. E., Perry, R. T., Bassett, S. S., Pletniková, O., Troncoso, J. C., Hardy, J., Singleton, A., & Traynor, B. J. (2012) · New England Journal of Medicine · doi:10.1056/nejmc1113592 · Cited by 168 · see citing works
Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease
Brouwers, N., Sleegers, K., Engelborghs, S., Maurer‐Stroh, S., Gijselinck, I., van der Zee, J., Pickut, B. A., den Broeck, M. V., Mattheijssens, M., Peeters, K., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000319688.89790.7a · Cited by 162 · see citing works
Brouwers, N., Nuytemans, K., van der Zee, J., Gijselinck, I., Engelborghs, S., Theuns, J., Kumar‐Singh, S., Pickut, B. A., Pals, P., Dermaut, B., et al. (2007) · Archives of Neurology · doi:10.1001/archneur.64.10.1436 · Cited by 150 · see citing works
The chromosome 9 ALS and FTD locus is probably derived from a single founder
Mok, K., Traynor, B. J., Schymick, J., Tienari, P. J., Laaksovirta, H., Peuralinna, T., Myllykangas, L., Chiò, A., Shatunov, A., Boeve, B. F., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.08.005 · Cited by 131 · see citing works
Self-citationAthan, E. S. (2001) · JAMA · doi:10.1001/jama.286.18.2257 · Cited by 106 · see citing works
Carecchio, M., Fenoglio, C., Riz, M. A. D., Guidi, I., Comi, C., Cortini, F., Venturelli, E., Restelli, I., Cantoni, C., Bresolin, N., et al. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.07.011 · Cited by 84 · see citing works
Alzheimer disease‐like clinical phenotype in a family with FTDP‐17 caused by a MAPT R406W mutation
Lindquist, S. G., Holm, I. E., Schwartz, M., Law, I. G., Stokholm, J., Batbayli, M., Waldemar, G., & Nielsen, J. E. (2008) · European Journal of Neurology · doi:10.1111/j.1468-1331.2008.02069.x · Cited by 80 · see citing works
Rademakers, R., Dermaut, B., Peeters, K., Cruts, M., Heutink, P., Goate, A., & Broeckhoven, C. V. (2003) · Human Mutation · doi:10.1002/humu.10269 · Cited by 75 · see citing works
Self-citationAlzheimer Disease–like Phenotype Associated With the c.154delA Mutation in Progranulin
Kelley, B. J., Haidar, W. N., Boeve, B. F., Baker, M. C., Shiung, M. S., Knopman, D. S., Rademakers, R., Hutton, M., Adamson, J. L., Kuntz, K. M., et al. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.113 · Cited by 66 · see citing works
Self-citationClinical and pathological features of an Alzheimer's disease patient with the MAPT ΔK280 mutation
Momeni, P., Pittman, A. M., Lashley, T., Vandrovcová, J., Malzer, E., Luk, C. Y., Hulette, C., Lees, A. J., Révész, T., Hardy, J., et al. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.07.013 · Cited by 66 · see citing works
Novel exon 1 progranulin gene variant in Alzheimer’s disease
Cortini, F., Fenoglio, C., Guidi, I., Venturelli, E., Pomati, S., Marcone, A., Scalabrini, D., Villa, C., Clerici, F., Valle, E. D., et al. (2008) · European Journal of Neurology · doi:10.1111/j.1468-1331.2008.02266.x · Cited by 56 · see citing works
The Tau R406W Mutation Causes Progressive Presenile Dementia with Bitemporal Atrophy
Ostojic, J., Elfgren, C., Passant, U., Nilsson, K., Gustafson, L., Lannfelt, L., & Fabre, S. F. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000077158 · Cited by 48 · see citing works
Brickell, K. L., Leverenz, J. B., Steinbart, E. J., Rumbaugh, M. C., Schellenberg, G. D., Nochlin, D., Lampe, T. H., Holm, I. E., Deerlin, V. M. V., Yuan, W., et al. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.113803 · Cited by 43 · see citing works
Self-citationAnalysis of the hexanucleotide repeat in C9ORF72 in Alzheimer's disease
Rollinson, S. J., Halliwell, N. A., Young, K., Callister, J. B., Toulson, G., Gibbons, L., Davidson, Y. S., Robinson, A., Gerhard, A., Richardson, A. M. T., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.01.109 · Cited by 41 · see citing works
Wallon, D., Rovelet‐Lecrux, A., Deramecourt, V., Pariente, J., Auriacombe, S., Ber, I. L., Schraen‐Maschke, S., Pasquier, F., Campion, D., & Hannequin, D. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120877 · Cited by 34 · see citing works
Dementia Mimicking Alzheimer's Disease Owing to a Tau Mutation: CSF and PET Findings
Tolboom, N., Koedam, E., Schott, J. M., Yaqub, M. M., Blankenstein, M. A., Barkhof, F., Pijnenburg, Y. A. L., Lammertsma, A. A., Scheltens, P., & van Berckel, B. N. M. (2010) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e3181cf35ec · Cited by 29 · see citing works
Genetic testing in familial AD and FTD: Mutation and phenotype spectrum in a Danish cohort
Lindquist, S. G., Schwartz, M., Batbayli, M., Waldemar, G., & Nielsen, J. (2009) · Clinical Genetics · doi:10.1111/j.1399-0004.2009.01191.x · Cited by 25 · see citing works
Novel exon 1 progranulin gene variant in Alzheimer's disease.
Cortini, F., Fenoglio, C., Venturelli, E., Pomati, S., Marcone, A., Scalabrini, D., Villa, C., Serpente, M., Clerici, F., Mariani, C. B., et al. (2009) · Cited by 7 · see citing works
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- [16]Cruchaga C Chakraventy S Mayo K Vallania FL Mitra A Faber KM Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer’s Disease families PLoS One 2012 In Press. PMC3270040 22312439
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Defeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676 · see citing works
Sareen, D., O’Rourke, J. G., Meera, P., Muhammad, A. K. M. G., Grant, S., Simpkinson, M., Bell, S., Carmona, S., Ornelas, L., Sahabian, A., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007529 · Cited by 670 · see citing works
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Cacace, R., Sleegers, K., & Van Broeckhoven, C. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.012 · Cited by 617 · see citing works
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Cruchaga, C., Karch, C. M., Jin, S. C., Benitez, B. A., Cai, Y., Guerreiro, R., Harari, O., Norton, J., Budde, J., Bertelsen, S., et al. (2014) · Nature · doi:10.1038/nature12825 · Cited by 461 · see citing works
Self-citationInteractions of pathological proteins in neurodegenerative diseases
Spires‐Jones, T. L., Attems, J., & Thal, D. R. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1709-7 · Cited by 424 · see citing works
Yu, L., Chibnik, L. B., Srivastava, G. P., Pochet, N., Yang, J., Xu, J., Kozubek, J., Obholzer, N., Leurgans, S. E., Schneider, J. A., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2014.3049 · Cited by 290 · see citing works
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Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine
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Self-citationC9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis
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Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
Mann, D. M., Rollinson, S., Robinson, A., Bennion Callister, J., Thompson, J. C., Snowden, J. S., Gendron, T., Petrucelli, L., Masuda-Suzukake, M., Hasegawa, M., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-68 · Cited by 182 · see citing works
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Liu, E. Y., Russ, J., Wu, K., Neal, D., Suh, E., McNally, A. G., Irwin, D. J., Van Deerlin, V. M., & Lee, E. B. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1286-y · Cited by 180 · see citing works
Cooper‐Knock, J., Shaw, P. J., & Kirby, J. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1251-9 · Cited by 163 · see citing works
Alzheimer's Disease Genetics Consortium, Wetzel-Smith, M. K., Hunkapiller, J., Bhangale, T. R., Srinivasan, K., Maloney, J. A., Atwal, J. K., Sa, S. M., B Yaylaoglu, M., Foreman, O., et al. (2014) · Nature Medicine · doi:10.1038/nm.3736 · Cited by 153 · see citing works
Self-citationC9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly
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Lall, D., Lorenzini, I., Mota, T. A., Bell, S., Mahan, T. E., Ulrich, J. D., Davtyan, H., Rexach, J. E., Muhammad, A. K. M. G., Shelest, O., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.020 · Cited by 147 · see citing works
Cruchaga, C., Del‐Aguila, J. L., Saef, B., Black, K., Fernandez, M. V., Budde, J., Ibanez, L., Deming, Y., Kapoor, M., Tosto, G., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.08.013 · Cited by 138 · see citing works
Self-citationHypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier
Russ, J., Liu, E. Y., Wu, K., Neal, D., Suh, E. R., Irwin, D. J., McMillan, C. T., Harms, M. B., Cairns, N. J., Wood, E. M., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1365-0 · Cited by 128 · see citing works
Self-citationRelationship between C9orf72 repeat size and clinical phenotype
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Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia
Benussi, A., Padovani, A., & Borroni, B. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00171 · Cited by 122 · see citing works
Davidson, Y. S., Barker, H., Robinson, A., Thompson, J. C., Harris, J., Troakes, C., Smith, B. N., Al‐Saraj, S., Shaw, C. E., Rollinson, S. J., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-70 · Cited by 115 · see citing works
Tomé, S. O., Vandenberghe, R. R., Ospitalieri, S., Schoor, E. V., Tousseyn, T., Otto, M., Arnim, C. A. F. V., & Thal, D. R. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00934-5 · Cited by 106 · see citing works
DeJesus‐Hernandez, M., Finch, N. A., Wang, X., Gendron, T. F., Bieniek, K. F., Heckman, M. G., Vasilevich, A. S., Murray, M. E., Rousseau, L., Weesner, R. E., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1725-7 · Cited by 92 · see citing works
Self-citationGenotype–phenotype links in frontotemporal lobar degeneration
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Ibáñez, L., Dube, U., Saef, B. A., Budde, J., Black, K., Medvedeva, A., Del‐Aguila, J. L., Davis, A. A., Perlmutter, J. S., Harari, O., et al. (2017) · BMC Neurology · doi:10.1186/s12883-017-0978-z · Cited by 83 · see citing works
Self-citationGenome-wide analysis of genetic predisposition to Alzheimer’s disease and related sex disparities
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Harms, M. B., Cady, J., Zaidman, C. M., Cooper, P., Bali, T., Allred, P., Cruchaga, C., Baughn, M. W., Libby, R. T., Pestronk, A., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.006 · Cited by 76 · see citing works
Self-citationHübers, A., Marroquin, N., Schmoll, B., Vielhaber, S., Just, M., Mayer, B., Högel, J., Dorst, J., Mertens, T., Just, W., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.034 · Cited by 69 · see citing works
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Update on amyotrophic lateral sclerosis genetics
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The C9ORF72 expansion mutation: gene structure, phenotypic and diagnostic issues
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Clinical Evidence of Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion
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Fratta, P., Polke, J. M., Newcombe, J., Mizielinska, S., Lashley, T., Poulter, M., Beck, J. A., Preza, E., Devoy, A., Sidle, K. C. L., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.037 · Cited by 61 · see citing works
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Bourinaris, T., & Houlden, H. (2018) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12677 · Cited by 54 · see citing works
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Unravelling the clinical spectrum and the role of repeat length in C9ORF72 repeat expansions
van der Ende, E. L., Jackson, J. L., White, A. E., Seelaar, H., van Blitterswijk, M., & Swieten, J. C. V. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-325377 · Cited by 52 · see citing works
Schottlaender, L., Polke, J. M., Ling, H., MacDoanld, N. D., Tucci, A., Nanji, T., Pittman, A. M., de Silva, R., Holton, J. L., Révész, T., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.024 · Cited by 49 · see citing works
Neuronal VCP loss of function recapitulates FTLD-TDP pathology
Wani, A., Zhu, J., Ulrich, J. D., Eteleeb, A. M., Sauerbeck, A. D., Reitz, S. J., Arhzaouy, K., Ikenaga, C., Yuede, C. M., Pittman, S. K., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109399 · Cited by 44 · see citing works
Self-citationParkinson disease is not associated with C9ORF72 repeat expansions
Harms, M. B., Neumann, D. A., Benítez, B. A., Cooper, B., Carrell, D., Racette, B. A., Perlmutter, J. S., Goate, A., & Cruchaga, C. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.10.001 · Cited by 43 · see citing works
Self-citationMarogianni, 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 · see citing works
Harms, M. B., & Baloh, R. H. (2013) · Neurologic Clinics · doi:10.1016/j.ncl.2013.05.003 · Cited by 40 · see citing works
Self-citationZhao, K., Chen, P., Alexander‐Bloch, A. F., Wei, Y., Dyrba, M., Yang, F., Kang, X., Wang, D., Fan, D., Shan, Y., et al. (2023) · EClinicalMedicine · doi:10.1016/j.eclinm.2023.102276 · Cited by 35 · see citing works
Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease
Fernández, M. V., Kim, J. H., Budde, J., Black, K., Medvedeva, A., Saef, B. A., Deming, Y. K., Del‐Aguila, J. L., Ibáñez, L., Dube, U., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1007045 · Cited by 34 · see citing works
Self-citationC9ORF72 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 33 · see citing works
The autophagy of stress granules
Ryan, L., & Rubinsztein, D. C. (2023) · FEBS Letters · doi:10.1002/1873-3468.14787 · Cited by 30 · see citing works
Emerging role of RNA•DNA hybrids inC9orf72-linked neurodegeneration
Wang, J., Haeusler, A. R., & Simko, E. A. J. (2015) · Cell Cycle · doi:10.1080/15384101.2014.995490 · Cited by 29 · see citing works
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 · see citing works
Self-citationC9orf72-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 · see citing works
The role of structural variations in Alzheimer’s disease and other neurodegenerative diseases
Wang, H., Wang, L., Schellenberg, G. D., & Lee, W. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1073905 · Cited by 25 · see citing works
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 24 · see citing works
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 · see citing works
C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation of Rag GTPases
Ji, Y. J., Ugolino, J., Zhang, T., Lu, J., Kim, D., & Wang, J. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008738 · Cited by 21 · see citing works
Reyes‐Dumeyer, D., Faber, K. M., Vardarajan, B. N., Goate, A., Renton, A. E., Chao, M., Boeve, B. F., Cruchaga, C., Pericak‐Vance, M. A., Haines, J. L., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12514 · Cited by 18 · see citing works
Self-citationFamilial 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 · see citing works
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 · see citing works
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 · see citing works
Excess of rare coding variants in PLD3 in late- but not early-onset Alzheimer’s disease
Schulte, E. C., Kurz, A., Alexopoulos, P., Hampel, H. J., Peters, A., Gieger, C., Rujescu, D., Diehl‐Schmid, J., & Winkelmann, J. (2015) · Human Genome Variation · doi:10.1038/hgv.2014.28 · Cited by 16 · see citing works
DNA Sequence Analysis in Clinical Medicine, Proceeding Cautiously
Smith, M. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00024 · Cited by 16 · see citing works
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 · see citing works
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 · see citing works
Self-citationConcordance Between 11 C-PIB-PET and Clinical Diagnosis in a Memory Clinic
Patricio, C. M., Cohen, G., Russo, J., Suarez, M. F., Nahas, F., Russo, G., Claudio, W., Santiago, P., Leonardo, T., Jorge, C., et al. (2015) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317515576387 · Cited by 13 · see citing works
Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case Studies
Foxe, D., Elan, E., Burrell, J. R., Leslie, F. V. C., Devenney, E. M., Kwok, J. B., Halliday, G. M., Hodges, J. R., & Piguet, O. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.01615 · Cited by 13 · see citing works
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 · see citing works
Cell-type specific differences in promoter activity of the ALS-linked C9orf72 mouse ortholog
Langseth, A. J., Kim, J., Ugolino, J., Shah, Y., Hwang, H., Wang, J., Bergles, D. E., & Brown, S. P. (2017) · Scientific Reports · doi:10.1038/s41598-017-05864-2 · Cited by 12 · see citing works
Distinct neurological disorders with C9orf72 mutations: genetics, pathogenesis, and therapy
Chi, S., Jiang, T., Tan, L., & Yu, J. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.033 · Cited by 11 · see citing works
Gagliardi, D., Costamagna, G., Taiana, M. M., Andreoli, L., Biella, F., Bersani, M., Bresolin, N., Comi, G. P., & Corti, S. P. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101172 · Cited by 11 · see citing works
Wei, Z., Iyer, M. R., Zhao, B., Deng, J., & Mitchell, C. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413450 · Cited by 10 · see citing works
Wang, M., Jiang, Y., & Huang, Z. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00796-4 · Cited by 9 · see citing works
C9orf72 repeat length might influence clinical sub-phenotypes in dementia patients
König, T., Wurm, R., Parvizi, T., Silvaieh, S., Hotzy, C., Çetin, H., Klotz, S., Gelpí, E., Bancher, C., Benke, T., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105927 · Cited by 9 · see citing works
Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion
Ber, I. L. (2015) · Revue Neurologique · doi:10.1016/j.neurol.2015.04.004 · Cited by 8 · see citing works
Qiao, J., Wang, T., Shao, Z., Zhu, Y., Zhang, M., Huang, S., & Zeng, P. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.12.012 · Cited by 8 · see citing works
Geiger, J. T., Arthur, K. C., Dawson, T. M., Rosenthal, L. S., Pantelyat, A. Y., Albert, M., Hillis, A. E., Crain, B. J., Pletniková, O., Troncoso, J. C., et al. (2016) · Neurodegenerative Diseases · doi:10.1159/000445872 · Cited by 8 · see citing works
Genetics of dementia in a Finnish cohort
Pasanen, P., Myllykangas, L., Pöyhönen, M., Kiviharju, A., Siitonen, M., Hardy, J., Brás, J., Paetau, A. E., Tienari, P. J., Guerreiro, R. J., et al. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-018-0117-3 · Cited by 8 · see citing works
Clinical Update on C9orf72: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and Beyond
Saracino, D., & Ber, I. L. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_5 · Cited by 7 · see citing works
Liang, Z., Wu, Y., Li, C., & Liu, Z. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1119326 · Cited by 6 · see citing works
Vinceti, G., Gallingani, C., Zucchi, E., Martinelli, I., Gianferrari, G., Simonini, C., Bedin, R., Chiari, A., Zamboni, G., & Mandrioli, J. (2023) · Genes · doi:10.3390/genes14040930 · Cited by 6 · see citing works
Zubizarreta, I. K., Manero-Azua, Á., Afonso-Agüera, J., & de Nanclares, G. P. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13091396 · Cited by 7 · see citing works
Mehrabian, S., Thonberg, H., Raycheva, M. R., Lilius, L., Stoyanova, K., Forsell, C., Cavallin, L., Nesheva, D. V., Westman, E., Toncheva, D. I., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0208383 · Cited by 6 · see citing works
Chandy, T. (2023) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2022-0025 · Cited by 4 · see citing works
Meta-analysis of the association between C9orf72 repeats and neurodegeneration diseases
Jin, P., Li, Y., & Li, Y. (2024) · Journal of Neurogenetics · doi:10.1080/01677063.2024.2343672 · Cited by 4 · see citing works
Gallucci, M., Dell’Acqua, C., Bergamelli, C., Fenoglio, C., Serpente, M., Galimberti, D., Fiore, V., Medea, S., Gregianin, M., & Battista, M. E. D. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180715 · Cited by 4 · see citing works
Li, Y., Geng, J., Rimal, S., Wang, H., Liu, X., Lu, B., & Li, S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.102995 · Cited by 4 · see citing works
Early-onset Alzheimer’s disease versus frontotemporal dementia: resolution with genetic diagnoses?
Sha, S. J., Khazenzon, A. M., Ghosh, P. M., Rankin, K. P., Pribadi, M., Coppola, G., Geschwind, D. H., Rabinovici, G. D., Miller, B. L., & Lee, S. E. (2015) · Neurocase · doi:10.1080/13554794.2015.1080283 · Cited by 3 · see citing works
Leskelä, S., Takalo, M., Marttinen, M., Huber, N., Paananen, J., Mitra, V., Rauramaa, T. H., Mäkinen, P. M., Leinonen, V., Soininen, H. S., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170362 · Cited by 3 · see citing works
Lucidi, G., Berti, V., Piaceri, I., Ginestroni, A., Lombardi, G., Ferrari, C., Polito, C., Bessi, V., Pupi, A., Nacmias, B., et al. (2019) · Neurology and Clinical Neuroscience · doi:10.1111/ncn3.12331 · Cited by 2 · see citing works
From the Genetic Code to Neuromics
Rosenberg, R. N. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.2854 · Cited by 1 · see citing works
Non‐Alzheimer's amnestic mild cognitive impairment with medial temporal hypometabolism
Keersmaecker, S. D., Meyer, S. D., & Vandenberghe, R. R. (2024) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.70018 · Cited by 1 · see citing works
C9ORF72 repeat expansion: a genetic mutation associated with Amyotrophic Lateral Sclerosis
Vats, K., Verma, M., Gourie‐Devi, M., & Taneja, V. (2014) · Current Medicine Research and Practice · doi:10.1016/j.cmrp.2014.07.002 · Cited by 1 · see citing works
C9ORF72: grabbing a tiger by the tail
Mann, D. M. A. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1252-8 · Cited by 1 · see citing works
Diversity of Cognitive Phenotypes Associated with C9ORF72 Hexanucleotide Expansion
Gómez‐Tortosa, E., Jurczynska, C. P., Serrano, S., Macías, E. F., Olivié, L., Gallego, J., Guerrero, R., Trujillo-Tiebas, M. J., Ayuso, C., Ruiz, P., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150922 · Cited by 1 · see citing works
Utilidad de la neuroimagen amiloidea en Neurología asistencial
Méndez, P. C., Cohen, G., Russo, M. J., Suarez, M. F., Nahas, F., Russo, G., Claudio, W., Paz, S., Leonardo, T., Campos, J., et al. (2014) · Neurología Argentina · doi:10.1016/j.neuarg.2014.02.003 · Cited by 1 · see citing works
[Studies on specific stains in paraproteinemia. I. Myeloma].
SEMPRINI, A., Valora, N., Rizza, O., Gf, M., & Bolognesi, G. (1963) · PubMed
Early-Onset Alzheimer’s Disease, APOE4 And C9orf72 Expansion: A Case Report
Enrique-Benedito, T., Senoret, V., Sanchis, M., Penacho, V., Caracuel, Z., Arrizabalaga, M., Campoy, M. B., & Alcaraz, L. A. (2024) · Annals of Case Reports · doi:10.29011/2574-7754.101812
Román, K. D., Cristalli, C. A. A., Surace, E. I., Mezmezian, M. B., Levy, A., Lovera, A. B., Turizo, C. R. C., Sorbara, M., y Rojas, M. M. E., Graviotto, H. G., et al. (2026) · Brain Pathology · doi:10.1111/bpa.70057
- Authors
- Harms, M., Benitez, B. A., Cairns, N., Cooper, B., Cooper, P., Mayo, K., Carrell, D., Faber, K., Williamson, J., Bird, T., Diaz-Arrastia, R., Foroud, T. M., Boeve, B. F., Graff-Radford, N. R., Mayeux, R., Chakraverty, S., Goate, A. M., Cruchaga, C., & NIA-LOAD/NCRAD Family Study Consortium, F. T.
- Affiliations
- Washington University in St. Louis (US)
- Indiana University Indianapolis (US)
- Columbia University (US)
- University of Washington (US)
- The University of Texas Southwestern Medical Center (US)
- Mayo Clinic (US)
- Corresponding author
- Cruchaga, Carlos
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2013-06-01
- Volume
- 70
- Issue
- 6
- Pages
- 736
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC3681841
- OpenAlex
- W2035247606
- Cited by
- 102
- References
- 33
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 9 · 2018: 6 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 19 · 2013: 11 · 2012: 1
- FWCI
- 10.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p30ns069329-02)
- National Institute on Aging (P50‐AG16574, U01AG06786, U01AG006786, R01 AG32306, R01AG035083, R01AG041797, P50AG008702, R01AG032306, P50AG005681, P30AG013846, P50AG005134, U24AG056270, U24AG021886, P30AG062421, P50AG016574)
- National Institute of Mental Health (R01MH060009)
- National Institute of Neurological Disorders and Stroke (P30-NS069329, K08NS075094)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- C9orf72, hexanucleotide repeat expansion, late-onset Alzheimer's disease, familial Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, genetic susceptibility, genetic screening, neuropathology
- MeSH terms
- C9orf72 Protein, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Pedigree, Proteins, Cohort Studies, Case-Control Studies, DNA Repeat Expansion
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