CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro
Open accessAbstract
The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of CHMP2B in Belgian patients (N = 146) identified one nonsense mutation in exon 5 (c.493C>T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in CHMP2B might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive.
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CHMP2B mutations were initially associated with rare cases of chromosome 3-linked familial FTD.
“CHMP2B mutations were initially associated with rare cases of chromosome 3-linked familial FTD [264,265]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [265]
CHMP2B downregulation or expression of disease-associated CHMP2B mutants in Drosophila and mammalian cell lines results in aberrant endosomal structures, impaired autophagosome maturation, and cytosolic TARDBP aggregates.
“CHMP2B downregulation or expression of disease-associated CHMP2B mutants in Drosophila and mammalian cell lines results in aberrant endosomal structures, impaired autophagosome maturation, and cytosolic TARDBP aggregates [264,265,268,269].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [265]
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Cites
Frontotemporal 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 · see citing works
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
Self-citationLitvan, I., Agid, Y., Calne, D., Campbell, G., Dubois, B., Duvoisin, R. C., Goetz, C. G., Golbe, L. I., Grafman, J., Growdon, J. H., et al. (1996) · Neurology · doi:10.1212/wnl.47.1.1 · Cited by 2,538 · see citing works
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Baker, M., Mackenzie, I. R., Pickering-Brown, S. M., Gass, J., Rademakers, R., Lindholm, C., Snowden, J., Adamson, J., Sadovnick, A. D., Rollinson, S., et al. (2006) · Nature · doi:10.1038/nature05016 · Cited by 2,058 · see citing works
Cruts, M., Gijselinck, I., van der Zee, J., Engelborghs, S., Wils, H., Pirici, D., Rademakers, R., Vandenberghe, R., Dermaut, B., Martin, J.-J., et al. (2006) · Nature · doi:10.1038/nature05017 · Cited by 1,512 · see citing works
Self-citationBabst, M., Katzmann, D. J., Estepa, E. J., Meerloo, T., & Emr, S. D. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00220-4 · Cited by 875 · see citing works
Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia
Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., et al. (2005) · Nature Genetics · doi:10.1038/ng1609 · Cited by 822 · see citing works
Self-citationThe Protein Network of HIV Budding
von Schwedler, U. K., Stuchell‐Brereton, M. D., Müller, B., Ward, D. M., Chung, H.-Y., Morita, E., Wang, H. E., Davis, T., He, G.-P., Cimbora, D. M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00714-1 · Cited by 815 · see citing works
Babst, M., Wendland, B., Estepa, E. J., & Emr, S. D. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.2982 · Cited by 770 · see citing works
Babst, M., Katzmann, D. J., Snyder, W. B., Wendland, B., & Emr, S. D. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00219-8 · Cited by 662 · see citing works
The evolution and pathology of frontotemporal dementia
Kertesz, A., McMonagle, P., Blair, M., Davidson, W., & Munoz, D. G. (2005) · Brain · doi:10.1093/brain/awh598 · Cited by 609 · see citing works
Neary, D., Snowden, J. S., & Mann, D. M. A. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70223-4 · Cited by 539 · see citing works
ESCRT-III Dysfunction Causes Autophagosome Accumulation and Neurodegeneration
Lee, J., Beigneux, A. P., Ahmad, S. T., Young, S. G., & Gao, F. (2007) · Current Biology · doi:10.1016/j.cub.2007.07.029 · Cited by 490 · see citing works
Frontotemporal dementia: Clinicopathological correlations
Forman, M. S., Farmer, J., Johnson, J. K., Clark, C. M., Arnold, S. E., Coslett, H. B., Chatterjee, A., Hurtig, H. I., Karlawish, J. H., Rosen, H. J., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20873 · Cited by 478 · see citing works
Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP
Josephs, K. A., Petersen, R. C., Knopman, D. S., Boeve, B. F., Whitwell, J. L., Duffy, J. R., Parisi, J. E., & Dickson, D. W. (2006) · Neurology · doi:10.1212/01.wnl.0000191307.69661.c3 · Cited by 455 · see citing works
Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations
Inoue, K., Khajavi, M., Ohyama, T., Hirabayashi, S.-I., Wilson, J., Reggin, J. D., Mancías, P., Butler, I. J., Wilkinson, M., Wegner, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1322 · Cited by 428 · see citing works
Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease
Khajavi, M., Inoue, K., & Lupski, J. R. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201649 · Cited by 420 · see citing works
Pathologic heterogeneity in clinically diagnosed corticobasal degeneration
Boeve, B. F., Maraganore, D. M., Parisi, J. E., Ahlskog, J. E., Graff-Radford, N., Caselli, R. J., Dickson, D. W., Kokmen, E., & Petersen, R. C. (1999) · Neurology · doi:10.1212/wnl.53.4.795 · Cited by 417 · see citing works
Accuracy of the Clinical Diagnosis of Corticobasal Degeneration
Litvan, I., Agid, Y., Goetz, C. G., Jankovic, J. J., Wenning, G. K., Brandel, J., Lai, E. C., Verny, M., Chaudhuri, К. R., McKee, A. C., et al. (1997) · Neurology · doi:10.1212/wnl.48.1.119 · Cited by 377 · see citing works
Babst, M. (2005) · Traffic · doi:10.1111/j.1600-0854.2004.00246.x · Cited by 376 · see citing works
novoSNP, a novel computational tool for sequence variation discoveryPreprint
Weckx, S., Del‐Favero, J., Rademakers, R., Claes, L. R. F., Cruts, M., Jonghe, P. D., Broeckhoven, C. V., & Rijk, P. D. (2005) · Genome Research · doi:10.1101/gr.2754005 · Cited by 285 · see citing works
Rieder, S., Banta, L. M., Köhrer, K., McCaffery, J. M., & Emr, S. D. (1996) · Molecular Biology of the Cell · doi:10.1091/mbc.7.6.985 · Cited by 280 · see citing works
Thompson, J. C. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.033779 · Cited by 251 · see citing works
Shim, S., Kimpler, L. A., & Hanson, P. I. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00584.x · Cited by 200 · see citing works
Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A
Scott, A., Gaspar, J., Stuchell‐Brereton, M. D., Alam, S. L., Skalicky, J. J., & Sundquist, W. I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502165102 · Cited by 183 · see citing works
Release of autoinhibition converts ESCRT-III components into potent inhibitors of HIV-1 budding
Zamborlini, A., Usami, Y., Radoshitzky, S. R., Popova, E. N., Palù, G., & Göttlinger, H. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603788103 · Cited by 178 · see citing works
Wilms, H., Sievers, J., & Deuschl, G. (1999) · Movement Disorders · doi:10.1002/1531-8257(199907)14:4 · Cited by 171 · see citing works
Familial non-specific dementia maps to chromosome 3
Brown, J., Ashworth, A., Gydesen, S., Sorensen, A., Rossor, M. N., Hardy, J., & Collinge, J. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.9.1625 · Cited by 162 · see citing works
Self-citationWhitley, P. R., Reaves, B. J., Hashimoto, M., Riley, A. M., Potter, B. V. L., & Holman, G. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306864200 · Cited by 160 · see citing works
Lin, Y., Kimpler, L. A., Naismith, T. V., Lauer, J. M., & Hanson, P. I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413968200 · Cited by 157 · see citing works
van der Zee, J., Ber, I. L., Maurer‐Stroh, S., Engelborghs, S., Gijselinck, I., Camuzat, A., Brouwers, N., Vandenberghe, R. R., Sleegers, K., Hannequin, D., et al. (2007) · Human Mutation · doi:10.1002/humu.9484 · Cited by 123 · see citing works
Self-citationCHMP4B, a Novel Gene for Autosomal Dominant Cataracts Linked to Chromosome 20q
Shiels, A., Bennett, T. M., Knopf, H. L. S., Yamada, K., Yoshiura, K.-I., Niikawa, N., Shim, S., & Hanson, P. I. (2007) · The American Journal of Human Genetics · doi:10.1086/519980 · Cited by 122 · see citing works
Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects
Engelborghs, S. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.8.1148 · Cited by 120 · see citing works
Self-citationCHMP2B mutations are not a common cause of frontotemporal lobar degeneration
Cannon, A. D., Baker, M., Boeve, B. F., Josephs, K. A., Knopman, D. S., Petersen, R. C., Parisi, J. E., Dickison, D., Adamson, J. L., Snowden, J. S., et al. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.12.056 · Cited by 62 · see citing works
Genetic Variability in CHMP2B and Frontotemporal Dementia
Momeni, P., Rogaeva, E. A., Deerlin, V. M. V., Yuan, W., Grafman, J. H., Tierney, M., Huey, E. D., Bell, J., Morris, C. M., Kalaria, R. N., et al. (2006) · Neurodegenerative Diseases · doi:10.1159/000094771 · Cited by 50 · see citing works
Rizzu, P., van Mil, S. E., Anar, B., Rosso, S. M., Kaat, L. D., Heutink, P., & Swieten, J. C. V. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30410 · Cited by 37 · see citing works
Frontotemporal Lobar Degeneration with Ubiquitin-Positive Inclusions: A Molecular Genetic Update
van der Zee, J., Gijselinck, I., Pirici, D. N., Kumar‐Singh, S., Cruts, M., & Broeckhoven, C. V. (2007) · Neurodegenerative Diseases · doi:10.1159/000101847 · Cited by 23 · see citing works
Momeni, P., Bell, J., Duckworth, J., Hutton, M., Mann, D. M. A., Pickering-Brown, S. M., & Hardy, J. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.06.065 · Cited by 14 · see citing works
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Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management
Piguet, O., Hornberger, M., Mioshi, E., & Hodges, J. R. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70299-4 · Cited by 496 · see citing works
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- Authors
- van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., Fisher, E. M., Collinge, J., Isaacs, A. M., & Van Broeckhoven, C.
- Affiliations
- MRC Prion Unit (GB)
- University of Antwerp (BE)
- Universitair Ziekenhuis Leuven (BE)
- Ghent University Hospital (BE)
- UCL Queen Square Institute of Neurology (GB)
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-10-22
- Volume
- 17
- Issue
- 2
- Pages
- 313-322
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2117026326
- Cited by
- 167
- References
- 39
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 12 · 2021: 10 · 2020: 14 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 2 · 2013: 9 · 2012: 13
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Neurosearch Antwerp
- Belgian Federal Science Policy Office
- Fonds Wetenschappelijk Onderzoek (P6/43)
- Universiteit Antwerpen
- Vlaamse regering
- Instituut Born-Bunge
- Medical Research Council
- Bijzonder Onderzoeksfonds UGent
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- CHMP2B, frontotemporal lobar degeneration, endosomal dysfunction, multivesicular bodies, cryptic splicing, nonsense mutation, missense mutations, pathophysiological mechanisms, Belgian patients
- MeSH terms
- Dementia, DNA Mutational Analysis, Female, Humans, Male, Mutation, Nerve Tissue Proteins, Neurons, Pedigree, Endosomes, Transfection, Mutagenesis, Site-Directed, Mutation, Missense, Cell Line, Tumor, Endosomal Sorting Complexes Required for Transport
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