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Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS
Open accessAbstract
Several families have been reported with autosomal-dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to chromosome 9p21. Here, we report an expansion of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p. This same repeat expansion was identified in the majority of our families with a combined FTD/ALS phenotype and TDP-43-based pathology. Analysis of extended clinical series found the C9ORF72 repeat expansion to be the most common genetic abnormality in both familial FTD (11.7%) and familial ALS (23.5%). The repeat expansion leads to the loss of one alternatively spliced C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.
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“The GGGGCC repeat expansion suppresses the production of C9ORF72 protein by inhibiting transcription (140, 153, 225, 369, 497, 520).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [140]
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In the citing paper
“Approximately 10% of ALS cases are familial with autosomal dominant inheritance of mutations reported in at least 15 genes, including to name a few SOD1 , TARDBP , FUS , ANG , and OPTN (11, 18, 174, 465), and an expanded hexanucleotide repeat of GGGGCC in a noncoding region of the C9ORF72 gene (140, 497).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [140]
In the citing paper
“They can also cross the BBB by upregulating the expression of tight junction proteins in the BBB with the assistance of endothelial cell monocarboxylate transport proteins (56).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [56]
In the citing paper
“The most common genes identified in clinical practice include SOD1, C9ORF72, TARDBP, FUS, and OPTNTD-P43 (55–57, 73, 74).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [56]
In the citing paper
“In 2011, the seminal discovery of disease-associated expansion mutations within the C9orf72 gene uncovered the most common genetic cause of inherited ALS and FTD, accounting for 23–47% of familial cases and 4–21% of sporadic disease.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [141]
In the citing paper
“Unaffected individuals carry 2–30 repeated stretches of GGGGCC within the first intron of the gene, but patients with C9orf72-associated ALS-FTD harbor several hundred to thousands of repeats [141,142].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [141]
In the citing paper
“Mutation in C9orf72 accounts for 40% of familial ALS and FTD cases.303,304”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [304]
In the citing paper
“C9orf72 intronic hexanucleotide repeat expansion (GGGGCC) was identified as the most common genetic cause of FTD and ALS.304,335”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [304]
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Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
Self-citationFrontotemporal lobar degeneration: A consensus on clinical diagnostic criteria
Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P. H., Albert, M., et al. (1998) · Neurology · doi:10.1212/wnl.51.6.1546 · Cited by 5,047
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
Weıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
Brook, J. D., McCurrach, M. E., Harley, H. G., Buckler, A., Church, D. M., Aburatani, H., Hunter, K. W., Stanton, V. P., Thirion, J., Hudson, T. J., et al. (1992) · Cell · doi:10.1016/0092-8674(92)90154-5 · Cited by 2,754
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630
Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6
Vance, C. A., Rogelj, B., Hortobágyi, T., Vos, K. J. D., Nishimura, A. L., Sreedharan, J., Hu, X., Smith, B. N., Ruddy, D., Wright, P. D., et al. (2009) · Science · doi:10.1126/science.1165942 · Cited by 2,625
Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis
Kwiatkowski, T. J., Bosco, D. A., LeClerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., Davis, A., Gilchrist, J. M., Kasarskis, E. J., Munsat, T. L., et al. (2009) · Science · doi:10.1126/science.1166066 · Cited by 2,624
Anderson, E. N. (1977) · eScholarship (California Digital Library) · Cited by 2,567
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Chiò, A., Calvo, A., Mazzini, L., Cantello, R. M., Mora, G., Moglia, C., Corrado, L., D’Alfonso, S., Majounie, E., Renton, A. E., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182735d36 · Cited by 171
Farg, M. A., Konopka, A., Soo, K. Y., Ito, D., & Atkin, J. D. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx170 · Cited by 173
Birger, A., Ben‐Dor, I., Ottolenghi, M., Turetsky, T. T., Gil, Y., Sweetat, S., Perez, L., Belzer, V., Casden, N., Steiner, D., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.11.026 · Cited by 164
C9orf72 repeat expansions are a rare genetic cause of parkinsonism
Lesage, S., Le Ber, I., Condroyer, C., Broussolle, E., Gabelle, A., Thobois, S., Pasquier, F., Mondon, K., Dion, P. A., Rochefort, D., et al. (2013) · Brain · doi:10.1093/brain/aws357 · Cited by 164
Molecular diagnostics of neurodegenerative disorders
Agrawal, M., & Biswas, A. (2015) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2015.00054 · Cited by 164
Dissection of genetic factors associated with amyotrophic lateral sclerosis
Leblond, C. S., Kaneb, H., Dion, P. A., & Rouleau, G. A. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.04.013 · Cited by 175
The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes
Schwenk, B. M., Lang, C. M., Hogl, S., Tahirović, S., Orozco, D., Rentzsch, K., Lichtenthaler, S. F., Hoogenraad, C. C., Capell, A., Haass, C., et al. (2013) · The EMBO Journal · doi:10.1002/embj.201385857 · Cited by 168
A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS–FTD
Irwin, K. E., Jasin, P., Braunstein, K. E., Sinha, I. R., Garret, M. A., Bowden, K. D., Chang, K., Troncoso, J. C., Moghekar, A., Oh, E. S., et al. (2024) · Nature Medicine · doi:10.1038/s41591-023-02788-5 · Cited by 200
Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum
Cruts, M., Gijselinck, I., Langenhove, T. V., van der Zee, J., & Broeckhoven, C. V. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.010 · Cited by 170
Campos‐Melo, D., Droppelmann, C. A., He, Z., Volkening, K., & Strong, M. J. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-26 · Cited by 169
The microglial component of amyotrophic lateral sclerosis
Clarke, B. E., & Patani, R. (2020) · Brain · doi:10.1093/brain/awaa309 · Cited by 164
Cooper‐Knock, J., Shaw, P. J., & Kirby, J. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1251-9 · Cited by 169
“Reduced expression of C9ORF72 mRNA is seen in the presence of the expansion [2].”
BackgroundInfluentialPoly-dipeptides encoded by the C9ORF72 repeats block global protein translation
Kanekura, K., Yagi, T., Cammack, A. J., Mahadevan, J., Kuroda, M., Harms, M. B., Miller, T. M., & Urano, F. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw052 · Cited by 165
RNA toxicity in non‐coding repeat expansion disorders
Swinnen, B., Robberecht, W., & Bosch, L. V. D. (2019) · The EMBO Journal · doi:10.15252/embj.2018101112 · Cited by 161
“The most frequent cause of ALS/FTD is a repeat expansion in the C9ORF72 gene (DeJesus-Hernandez et al, 2011; Renton et al, 2011, 2014).”
Umoh, M. E., Dammer, E. B., Dai, J., Duong, D. M., Lah, J. J., Levey, A. I., Gearing, M., Glass, J. D., & Seyfried, N. T. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201708202 · Cited by 159
Disrupted neuronal trafficking in amyotrophic lateral sclerosis
Burk, K., & Pasterkamp, R. J. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01964-7 · Cited by 162
Noncoding RNAs in neurodegeneration
Salta, E., & De Strooper, B. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.90 · Cited by 183
SOD1 in Amyotrophic Lateral Sclerosis: “Ambivalent” Behavior Connected to the Disease
Pansarasa, O., Bordoni, M., Diamanti, L., Sproviero, D., Gagliardi, S., & Cereda, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051345 · Cited by 170
“C9orf72 [12,13] and recently TBK1 [14,15] have all been indicated as causes of ALS.”
Backgroundp53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR)
Maor-Nof, M., Shipony, Z., Lopez-Gonzalez, R., Nakayama, L., Zhang, Y., Couthouis, J., Blum, J. A., Castruita, P. A., Linares, G. R., Ruan, K., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.025 · Cited by 161
“One way is by loss of function, resulting from decreased C9orf72 expression (DeJesus-Hernandez et al., 2011; Kim et al., 2020).”
Self-citationPeripheral monocytes are functionally altered and invade the CNS in ALS patients
Zondler, L., Müller, K., Khalaji, S., Bliederhäuser, C., Ruf, W. P., Grozdanov, V., Thiemann, M., Fundel-Clemes, K., Freischmidt, A., Holzmann, K., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1548-y · Cited by 154
“Analysis of the C9orf72 repeat length was performed by fragment length analysis and repeat-primed PCR using the previously published primers [21, 57] according to Hübers et al.”
Chew, J., Cook, C. N., Gendron, T. F., Jansen‐West, K. R., del Rosso, G., Daughrity, L. M., Castanedes‐Casey, M., Kurti, A., Stankowski, J. N., Disney, M. D., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0310-z · Cited by 160
Self-citationAltered network connectivity in frontotemporal dementia with C9orf72 hexanucleotide repeat expansion
Lee, S. E., Khazenzon, A. M., Trujillo, A. J., Guo, C. C., Yokoyama, J. S., Sha, S. J., Takada, L. T., Karydas, A. M., Block, N., Coppola, G., et al. (2014) · Brain · doi:10.1093/brain/awu248 · Cited by 165
Self-citationLillo, P., Mioshi, E., & Hodges, J. R. (2012) · BMC Neurology · doi:10.1186/1471-2377-12-156 · Cited by 157
“Caregiver burden seems to be closely coupled with the * Correspondence: e.mioshi@neura.edu.au 1Neuroscience Research Australia, Sydney, Australia 2School of Medical Sciences, University of New South Wales, Sydney, Australia Full list of author information is available at the end of the article © 2012 Lillo et al.; lic…”
InfluentialStewart, H. G., Rutherford, N. J., Briemberg, H., Krieger, C., Cashman, N. R., Fabros, M., Baker, M. C., Fok, A., DeJesus‐Hernandez, M., Eisen, A., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0937-5 · Cited by 156
Self-citationStress granule mediated protein aggregation and underlying gene defects in the FTD-ALS spectrum
Baradaran‐Heravi, Y., Broeckhoven, C. V., & van der Zee, J. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104639 · Cited by 165
G4C2 Repeat RNA Initiates a POM121-Mediated Reduction in Specific Nucleoporins in C9orf72 ALS/FTD
Coyne, A. N., Zaepfel, B. L., Hayes, L., Fitchman, B., Salzberg, Y., Luo, E.-C., Bowen, K., Trost, H., Aigner, S., Rigo, F., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.027 · Cited by 156
Rodent models of amyotrophic lateral sclerosis
McGoldrick, P., Joyce, P. I., Fisher, E., & Greensmith, L. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.03.012 · Cited by 162
Genetics of Frontotemporal Dementia
Olszewska, D. A., Lonergan, R., Fallon, E., & Lynch, T. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0707-9 · Cited by 170
TDP-43 frontotemporal lobar degeneration and autoimmune disease
Miller, Z. A., Rankin, K. P., Graff-Radford, N. R., Takada, L. T., Sturm, V. E., Cleveland, C. M., Criswell, L. A., Jaeger, P. A., Stan, T., Heggeli, K. A., et al. (2013) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-304644 · Cited by 170
Self-citationBoylan, K., Glass, J. D., Crook, J. E., Yang, C., Thomas, C. S., Desaro, P., Johnston, A., Overstreet, K., Kelly, C. M., Polak, M. A., et al. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303768 · Cited by 156
Self-citationAstrocytes and Microglia as Non-cell Autonomous Players in the Pathogenesis of ALS
Lee, J.-H., Hyeon, S. J., Im, H., Ryu, H., Kim, Y., & Ryu, H. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.5.233 · Cited by 160
A genomic view of short tandem repeats
Gymrek, M. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.01.012 · Cited by 161
Genetics of FTLD : overview and what else we can expect from genetic studies
Pottier, C., Ravenscroft, T. A., Sanchez‐Contreras, M., & Rademakers, R. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13622 · Cited by 148
“The GGGGCC hexanucleotide repeat is located between two 5’ non-coding exons of C9orf72 which encodes a largely uncharacterized protein with homology to differentially expressed in normal and neoplasia (DENN) proteins (DeJesus-Hernandez et al. 2011, Levine et al. 2013).”
BackgroundSelf-citationReview: neuropathology of non-tau frontotemporal lobar degeneration
Neumann, M., & Mackenzie, I. R. A. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12526 · Cited by 144
Self-citationTMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia
van Blitterswijk, M., Mullen, B., Nicholson, A. M., Bieniek, K. F., Heckman, M. G., Baker, M., DeJesus‐Hernandez, M., Finch, N. A., Brown, P. H., Murray, M. E., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1240-4 · Cited by 154
Self-citationInce, P. G., Highley, J. R., Kirby, J., Wharton, S. B., Takahashi, H., Strong, M. J., & Shaw, P. J. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0913-0 · Cited by 154
Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis
Shang, Y., & Huang, E. J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.036 · Cited by 164
Irwin, D. J., McMillan, C. T., Brettschneider, J., Libon, D. J., Powers, J., Rascovsky, K., Toledo, J. B., Boller, A., Bekisz, J. M., Chandrasekaran, K., et al. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303507 · Cited by 160
RNA G-quadruplexes and their potential regulatory roles in translation
Song, J., Perreault, J., Topisirović, I., & Richard, S. (2016) · Translation · doi:10.1080/21690731.2016.1244031 · Cited by 157
“C9orf72, a disease-related gene, harbors the expansion of a (GGGGCC)n(GGCCCC)n repeats within the first intron, leading to amyotrophic lateral sclerosis and frontotemporal dementia.(114,115) It e1244031-6 J.”
BackgroundMembrane trafficking in health and disease
Yarwood, R., Hellicar, J., Woodman, P. G., & Lowe, M. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.043448 · Cited by 161
“FTD and ALS: a tale of two diseases.”
BackgroundInfluentialStructural and functional brain connectivity in presymptomatic familial frontotemporal dementia
Dopper, E. G. P., Rombouts, S. A. R. B., Jiskoot, L. C., den Heijer, T., de Graaf, J. R. A., de Koning, I., Hammerschlag, A. R., Seelaar, H., Seeley, W. W., Veer, I. M., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000583 · Cited by 152
Self-citationSystemic dysregulation of TDP-43 binding microRNAs in amyotrophic lateral sclerosis
Freischmidt, A., Müller, K., Ludolph, A. C., & Weishaupt, J. H. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-42 · Cited by 158
“To date, hundreds of mutations in more than 20 genes have been implicated in the pathology of ALS, whereby mutations in genes coding for superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) as well as a hexanucleotide expansion on chromosome 9 in open reading frame 72 (C9ORF72)…”
BackgroundALS-associated mutations in FUS disrupt the axonal distribution and function of SMN
Groen, E. J. N., Fumoto, K., Blokhuis, A. M., Engelen-Lee, J.-Y., Zhou, Y., van den Heuvel, D. M. A., Koppers, M., van Diggelen, F., van Heest, J., Demmers, J., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt222 · Cited by 153
Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype
Mann, D. M. A., & Snowden, J. S. (2017) · Brain Pathology · doi:10.1111/bpa.12486 · Cited by 163
Age-related penetrance of the C9orf72 repeat expansion
Murphy, N. A., Arthur, K. C., Tienari, P. J., Houlden, H., Chiò, A., & Traynor, B. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-02364-1 · Cited by 152
Archbold, H. C., Jackson, K. L., Arora, A., Weskamp, K., Tank, E. M. H., Li, X., Miguez, R., Dayton, R. D., Tamir, S., Klein, R. L., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-22858-w · Cited by 157
Frontotemporal Dementia: Implications for Understanding Alzheimer DiseasePreprint
Goedert, M., Ghetti, B. F., & Spillantini, M. G. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006254 · Cited by 156
Dupuis, L., Dengler, R., Heneka, M. T., Meyer, T., Zierz, S., Kassubek, J., Fischer, W., Steiner, F., Lindauer, E., Otto, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037885 · Cited by 159
Endocytic membrane trafficking and neurodegenerative disease
Schreij, A. M. A., Fon, E. A., & McPherson, P. S. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2105-x · Cited by 160
There has been an awakening: Emerging mechanisms of C9orf72 mutations in FTD/ALS
Gitler, A. D., & Tsuiji, H. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.004 · Cited by 155
From animal models to human disease: a genetic approach for personalized medicine in ALS
Picher‐Martel, V., Valdmanis, P. N., Gould, P. V., Julien, J., & Dupré, N. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0340-5 · Cited by 163
“Specific disease characteristics in humans A hexanucleotide (GGGGCC) repeat in a non-coding region of C9orf72 was first described in 2011 in ALS, FTD and ALS-FTD familial cases [159, 160].”
BackgroundC9ORF72 interaction with cofilin modulates actin dynamics in motor neurons
Sivadasan, R., Hornburg, D., Drepper, C., Frank, N., Jablonka, S., Hansel, A., Lojewski, X., Sterneckert, J. L., Hermann, A., Shaw, P. J., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4407 · Cited by 155
Neuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments
Jung, Y. J., Tweedie, D., Scerba, M. T., & Greig, N. H. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00313 · Cited by 156
Cheng, W., Wang, S., Zhang, Z., Morgens, D. W., Hayes, L. R., Lee, S., Portz, B., Xie, Y., Nguyen, B. V., Haney, M. S., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.09.003 · Cited by 138
Exome sequencing to identify de novo mutations in sporadic ALS trios
Chesi, A., Staahl, B. T., Jovičić, A., Couthouis, J., Fasolino, M., Raphael, A. R., Yamazaki, T., Elias, L., Polak, M. A., Kelly, C. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3412 · Cited by 149
Abnormal RNA stability in amyotrophic lateral sclerosis
Tank, E., Figueroa‐Romero, C., Hinder, L. M., Bedi, K., Archbold, H. C., Li, X., Weskamp, K., Safren, N., Paez-Colasante, X., Pacut, C. M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05049-z · Cited by 153
Prion-Like Propagation of Protein Misfolding and Aggregation in Amyotrophic Lateral Sclerosis
McAlary, L., Plotkin, S. S., Yerbury, J. J., & Cashman, N. R. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00262 · Cited by 160
“Furthermore, the most common identified cause for fALS are hexanucleotide (GGGGCC) repeat expansions in the chromosome 9 open reading frame 72 (C9orf72) gene (DeJesus-Hernandez et al., 2011; Renton et al., 2011), that potentially lead to toxicity caused by the synthesis of large non-coding RNAs that form sense and ant…”
BackgroundInvited Review: The role of prion‐like mechanisms in neurodegenerative diseases
Jaunmuktane, Z., & Brandner, S. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12592 · Cited by 153
Boivin, M., Pfister, V., Gaucherot, A., Ruffenach, F., Negroni, L., Sellier, C., & Charlet‐Berguerand, N. (2020) · The EMBO Journal · doi:10.15252/embj.2018100574 · Cited by 137
“…expansion of GGGGCC (G4C2) repeats within the first intron of the C9ORF72 gene as the most common inherited cause for both ALS and FTD in Caucasian populations of northern Europe and North America (DeJesus-Hernandez et al , 2011; Renton et al , 2011; Gijselinck et al , 2012; Majounie et al , 2012).”
Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases
Chang, A., Xiang, X., Wang, J., Lee, C., Arakhamia, T., Simjanoska, M., Wang, C., Carlomagno, Y., Zhang, G., Dhingra, S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.02.026 · Cited by 150
“Sanger sequencing analysis of all exons of theGRN gene and expansion analysis of the GGGGCC repeat in C9orf72 using the 2-step protocol was performed in all FTLD-TDP cases as described previously (Baker et al., 2006; DeJesus-Hernandez et al., 2011).”
MethodSelf-citationOn-chip 3D neuromuscular model for drug screening and precision medicine in neuromuscular disease
Osaki, T., Uzel, S. G. M., & Kamm, R. D. (2020) · Nature Protocols · doi:10.1038/s41596-019-0248-1 · Cited by 152
C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly
Wang, T., Liu, H., Itoh, K., Oh, S., Zhao, L., Murata, D., Sesaki, H., Härtung, T., Na, C. H., & Wang, J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.005 · Cited by 154
Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD
Pineda, S. S., Lee, H., Fitzwalter, B. E., Mohammadi, S., Pregent, L., Gardashli, M., Mantero, J. C., Engelberg-Cook, E., DeJesus‐Hernandez, M., van Blitterswijk, M., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.031 · Cited by 158
Self-citationSOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS
Hayashi, Y., Homma, K., & Ichijo, H. (2015) · Advances in Biological Regulation · doi:10.1016/j.jbior.2015.10.006 · Cited by 161
Marangi, G., & Traynor, B. J. (2014) · Brain Research · doi:10.1016/j.brainres.2014.10.009 · Cited by 155
The clinical spectrum of sporadic and familial forms of frontotemporal dementia
Woollacott, I., & Rohrer, J. D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13654 · Cited by 163
“In 2011, two groups identified a hexanucleotide repeat expansion mutation in a non-coding region of the C9ORF72 gene (DeJesus-Hernandez et al. 2011; Renton et al. 2011).”
BackgroundInfluentialAutophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand
Ramesh, N., & Pandey, U. B. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00263 · Cited by 161
G-Quadruplexes as pathogenic drivers in neurodegenerative disorders
Wang, E., Thombre, R., Shah, Y., Latanich, R., & Wang, J. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab164 · Cited by 152
“The most common cause of ALS-FTD is a hexanucleotide repeat expansion (HRE), (GGGGCC)n, in a non-coding region of the chromosome 9 open reading frame 72 (C9orf72) gene (32,33).”
BackgroundValue of 18 Fluorodeoxyglucose–Positron-Emission Tomography in Amyotrophic Lateral Sclerosis
Laere, K. V., Vanhee, A., Verschueren, J., Coster, L. D., Driesen, A., Dupont, P. J., Robberecht, W., & Damme, P. V. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.62 · Cited by 147
Characterization of the dipeptide repeat protein in the molecular pathogenesis of c9FTD/ALS
Yamakawa, M., Ito, D., Honda, T., Kubo, K., Noda, M., Nakajima, K., & Suzuki, N. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu576 · Cited by 154
Molecular and Cellular Mechanisms Affected in ALS
Gall, L. L., Anakor, E., Connolly, O., Vijayakumar, U. G., Duddy, W. J., & Duguez, S. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030101 · Cited by 152
C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation
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
Self-citationNon-neuronal cells in amyotrophic lateral sclerosis — from pathogenesis to biomarkers
Vahsen, B. F., Gray, E., Thompson, A. G., Ansorge, O., Anthony, D. C., Cowley, S. A., Talbot, K., & Turner, M. R. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00487-8 · Cited by 147
Neuroimaging in Amyotrophic Lateral Sclerosis
Turner, M. R., Agosta, F., Bede, P., Govind, V., Lulé, D. E., & Verstraete, E. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.26 · Cited by 152
Bertrand, A., Wen, J., Rinaldi, D., Houot, M., Sayah, S., Camuzat, A., Fournier, C., Fontanella, S., Routier, A., Couratier, P., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4266 · Cited by 161
“F rontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)areneurodegenerativediseases with common genetic causes, the most frequent being aGGGGCC repeat expansion in the chromosome9open reading frame 72 (C9orf72) gene.(1,2) This expansion may lead toa lossofC9orf72 functionandcauses abnormalneu…”
Lifetime physical activity and the risk of amyotrophic lateral sclerosis
Huisman, M. H. B., Seelen, M., de Jong, S. W., Dorresteijn, K. R. I. S., van Doormaal, P. T. C., van der Kooi, A. J., de Visser, M., Schelhaas, H. J., van den Berg, L. H., & Veldink, J. H. (2013) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-304724 · Cited by 156
Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study
Kioumourtzoglou, M.-A., Rotem, R. S., Seals, R. M., Gredal, O., Hansen, J., & Weisskopf, M. G. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.0910 · Cited by 145
Does interneuronal dysfunction contribute to neurodegeneration in amyotrophic lateral sclerosis?
Turner, M. R., & Kiernan, M. C. (2012) · Amyotrophic Lateral Sclerosis · doi:10.3109/17482968.2011.636050 · Cited by 144
Waller, R., Goodall, G., Milo, M., Cooper‐Knock, J., Costa, M. D., Hobson, E., Kazoka, M., Wollff, H., Heath, P. R., Shaw, P. J., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.03.027 · Cited by 148
A novel mutation in VCP causes Charcot–Marie–Tooth Type 2 disease
Gonzalez, M., Feely, S. M. E., Speziani, F., Strickland, A. V., Danzi, M. C., Bacon, C. J., Lee, Y., Chou, T., Blanton, S. H., Weihl, C. C., et al. (2014) · Brain · doi:10.1093/brain/awu224 · Cited by 147
“sporadic ALS and unique VCP variants (DeJesus-Hernandez et al., 2011; Abramzon et al., 2012; Koppers et al., 2013).”
Mechanisms of toxicity in C9FTLD/ALS
Gendron, T. F., Belzil, V., Zhang, Y., & Petrucelli, L. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1237-z · Cited by 154
A Solid-State Conceptualization of Information Transfer from Gene to Message to Protein
Kato, M., & McKnight, S. L. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044700 · Cited by 147
Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease
Lindquist, S., Duno, M., Batbayli, M., Puschmann, A., Braendgaard, H., Mardosiene, S., Svenstrup, K., Pinborg, L., Vestergaard, K., Hjermind, L., et al. (2013) · Clinical Genetics · doi:10.1111/j.1399-0004.2012.01903.x · Cited by 143
“The expansion was identified in 46% of familial ALS and 21% of sporadic ALS in the Finnish population and in one third of familial ALS cases in an outbred European cohort (4, 5).”
BackgroundFunctional roles of alternative splicing factors in human disease
Cieply, B. W., & Carstens, R. P. (2015) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1276 · Cited by 148
Retroviruses and amyotrophic lateral sclerosis
Alfahad, T. B., & Nath, A. (2013) · Antiviral Research · doi:10.1016/j.antiviral.2013.05.006 · Cited by 144
Gallagher, M. D., Suh, E. R., Grossman, M., Elman, L. B., McCluskey, L. F., Swieten, J. C. V., Al‐Sarraj, S., Neumann, M., Gelpí, E., Ghetti, B. F., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1239-x · Cited by 148
“The function(s) of C9orf72 and its role in disease are currently areas of ongoing research [10], with evidence for both loss-of-function [8,11,15,28] and gain-of-toxic-function [1,13,25] mechanisms.”
BackgroundMethodInfluentialALS and other motor neuron diseases
Tiryaki, E., & Horak, H. A. (2014) · Continuum · doi:10.1212/01.con.0000455886.14298.a4 · Cited by 143
Repeat-associated non-ATG (RAN) translation in neurological disease
Cleary, J. D., & Ranum, L. P. W. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt371 · Cited by 149
“Consistent with this prediction, RAN translation has recently been reported in two additional disorders: fragile X-associated tremor ataxia syndrome (FXTAS) (24) and C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) (25–27).”
InfluentialTherapy and clinical trials in frontotemporal dementia: past, present, and future
Tsai, R. M., & Boxer, A. L. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13640 · Cited by 157
“In 2011, a hexanucleotide repeat expansion in the 5 0 non-coding region of the C9ORF72 gene was found to be the cause of FTD and ALS in a strongly chromosome 9p linked family (Boxer et al. 2011; DeJesus-Hernandez et al. 2011; Renton et al. 2011).”
Self-citationHautbergue, G. M., Castelli, L. M., Ferraiuolo, L., Sánchez-Martínez, Á., Cooper‐Knock, J., Higginbottom, A., Lin, Y.-H., Bauer, C. S., Dodd, J. E., Myszczynska, M. A., et al. (2017) · Nature Communications · doi:10.1038/ncomms16063 · Cited by 140
Wallings, R. L., Humble, S. W., Ward, M. E., & Wade-Martins, R. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.10.002 · Cited by 153
“Mutations in SQSTM1/p62 can be causal for both FTD and ALS, and its presence in protein inclusions is a pathognomonic signature in the disease spectrum [44].”
BackgroundInfluentialMacroautophagy in CNS health and disease
Griffey, C. J., & Yamamoto, A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00588-3 · Cited by 147
Development and Validation of Pedigree Classification Criteria for Frontotemporal Lobar Degeneration
Wood, E. M., Falcone, D., Suh, E. R., Irwin, D. J., Chen‐Plotkin, A. S., Lee, E. B., Xie, S. X., Deerlin, V. M. V., & Grossman, M. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.3956 · Cited by 146
Downregulation of MicroRNA-9 in iPSC-Derived Neurons of FTD/ALS Patients with TDP-43 Mutations
Zhang, Z., Almeida, S., Lu, Y., Nishimura, A. L., Peng, L., Sun, D., Wu, B., Karydas, A. M., Tartaglia, M. C., Fong, J. C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076055 · Cited by 142
Self-citationTDP-43/FUS in motor neuron disease: Complexity and challenges
Guerrero, E. N., Wang, H., Mitra, J., Hegde, P. M., Stowell, S. E., Liachko, N. F., Kraemer, B. C., Garruto, R. M., Rao, K. S. J., & Hegde, M. L. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.09.004 · Cited by 146
Tabet, R., Schaeffer, L., Freyermuth, F., Jambeau, M., Workman, M. J., Lee, C.-Z., Lin, C.-C., Jiang, J., Jansen‐West, K. R., Hamdan, H. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02643-5 · Cited by 144
RNA Toxicity and Missplicing in the Common Eye Disease Fuchs Endothelial Corneal Dystrophy
Du, J., Aleff, R. A., Soragni, E., Kalari, K. R., Nie, J. J., Tang, X., Davila, J. I., Kocher, J.-P. A., Patel, S. V., Gottesfeld, J. M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.621607 · Cited by 141
Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities
Sbodio, J. I., Snyder, S. H., & Paul, B. D. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7321 · Cited by 149
“One of the leading causes of ALS as well as frontotemporal dementia (FTD) is a mutation in the noncoding region of the chromosome 9 open reading frame 72 (C9ORF72) locus, where an expansion of the hexanucleotide GGGGCC occurs (125, 201, 324, 421).”
BackgroundFautsch, M. P., Wieben, E. D., Baratz, K. H., Bhattacharyya, N., Sadan, A. N., Hafford‐Tear, N. J., Tuft, S. J., & Davidson, A. E. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100883 · Cited by 148
Bede, P., Bokde, A. L. W., Elamin, M., Byrne, S., McLaughlin, R. L., Jordan, N., Hampel, H. J., Gallagher, L. B., Lynch, C. M., Fagan, A. J., et al. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-302674 · Cited by 141
Metadata
- Authors
- 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., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G.-Y. R., Karydas, A., Seeley, W. W., Josephs, K. A., Coppola, G., Geschwind, D. H., Wszolek, Z. K., Feldman, H., Knopman, D. S., Petersen, R. C., Miller, B. L., Dickson, D. W., Boylan, K. B., Graff-Radford, N. R., & Rademakers, R.
- Affiliations
- University of British Columbia (CA)
- Mayo Clinic (US)
- University of California, San Francisco (US)
- Mayo Clinic in Florida (US)
- University of California, Los Angeles (US)
- Corresponding author
- Mackenzie, Ian R.
- Rademakers, Rosa
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 72
- Issue
- 2
- Pages
- 245-256
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3202986
- OpenAlex
- W2154945114
- Semantic Scholar
- a14363772a9926a299f67b9fdebfb404d9b6100d
- Cited by
- 4,936
- References
- 58
- Citations by year
- 2026: 192 · 2025: 241 · 2024: 298 · 2023: 327 · 2022: 348 · 2021: 407 · 2020: 383 · 2019: 338 · 2018: 342 · 2017: 338 · 2016: 324 · 2015: 354 · 2014: 330 · 2013: 349 · 2012: 310
- FWCI
- 209.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P50 AG016574)
- National Institute of Neurological Disorders and Stroke (NS057567, 1RC2NS070276, P50NS072187)
- Canadian Institutes of Health Research (74580, 179009)
- Dystonia Medical Research Foundation
- Amyotrophic Lateral Sclerosis Association
- Mayo Foundation for Medical Education and Research
- National Institutes of Health (R01 AG026251, R01 AG037491, R01 NS065782)
- Larry L. Hillblom Foundation (P50 AG1657303)
- Mayo Clinic (U01 AG006786)
- 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, frontotemporal dementia, amyotrophic lateral sclerosis, chromosome 9p21, TDP-43 pathology, alternative splicing, familial neurodegenerative disease, genetic linkage
- MeSH terms
- C9orf72 Protein, Alleles, Amyotrophic Lateral Sclerosis, Chromosomes, Human, Pair 9, Female, Genotype, Haplotypes, Humans, Male, Pedigree, Proteins, Microsatellite Repeats, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, DNA Repeat Expansion, Frontotemporal Dementia
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