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Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement
Open accessAbstract
OBJECTIVE: To identify new genes and risk factors associated with frontotemporal dementia (FTD). Several genes and loci have been associated with different forms of FTD, but a large number of families with dementia do not harbor mutations in these genes. DESIGN: Whole-exome sequencing and whole-genome genotyping were performed in all patients. Genetic variants obtained from whole-exome sequencing were integrated with the data obtained from whole-genome genotyping. SETTING: Database of the Behavioral Neurology Outpatient Clinic of the Department of Neurology, Istanbul Faculty of Medicine, Istanbul, Turkey. PATIENTS Forty-four Turkish patients with an FTD-like clinical diagnosis were included in the study. Relatives were screened when appropriate. MAIN OUTCOME MEASURE: Mutations in the triggering receptor expressed on myeloid cells 2 gene (TREM2). RESULTS: In 3 probands with FTD-like disease, we identified different homozygous mutations in TREM2 that had previously been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). None of these 3 patients had a typical clinical presentation of PLOSL: they presented with behavioral change and subsequent cognitive impairment and motor features but without any bone cysts or bone-associated phenotypes. Imaging showed white matter abnormalities as well as frontal atrophy in all 3 patients. CONCLUSIONS: Our results show that TREM2 is responsible for an unexpectedly high number of dementia cases in our cohort, suggesting that this gene should be taken into account when mutations in other dementia genes are excluded. Even for complex syndromes such as dementia, exome sequencing has proven to be a rapid and cost-effective tool to identify genetic mutations, allowing for the association of clinical phenotypes with unexpected molecular underpinnings.
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“Nonsense or missense mutations in TREM2 have been identified in several families with FTD.343–345”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [344]
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“In addition to the R47H variant, further TREM2 variants have been revealed to be risk factors of AD or other CNS diseases, such as R62H (8,20), H157Y (25), Q33X, T66M and Y38C (26,27).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [27]
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“In particular, there is converging evidence for the role of neuroinflammation in neurodegenerative dementias, including FTD, from genetic associations (Guerreiro et al., 2013; Rayaprolu et al., 2013; Broce et al., 2018), CSF (Sjogren et al., 2004; Woollacott et al., 2018), epidemiology (Miller et al., 2013, 2016), post-mortem tissue (Venneti et al., 2008; Lant et al., 2014) and animal models”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Guerreiro et al., 2013
In the citing paper
“Homozygous TREM2 p.T66M mutation has also been identified to cause FTD-like syndrome.344”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [344]
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Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,508
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G. P., Onyike, C. U., et al. (2011) · Brain · doi:10.1093/brain/awr179 · Cited by 5,221
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
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-citationAssociation 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
Self-citationWeıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
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
Exome sequencing identifies the cause of a mendelian disorder
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., Huff, C. D., Shannon, P. T., Jabs, E. W., Nickerson, D. A., et al. (2010) · Nature Genetics · doi:10.1038/ng.499 · Cited by 1,957
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
Bouchon, A., Dietrich, J., & Colonna, M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.4991 · Cited by 1,284 · cited 1×
“It may be involved in chronic inflammation by triggering the production of constitutive rather than inflammatory chemokines and cytokines.(22) Interestingly, mutations in both these genes have been associated with PLOSL or Nasu-Hakola disease.”
A Human Genome Diversity Cell Line Panel
Cann, H. M., de Toma, C., Cazes, L., Legrand, M.-F., Morel, V., Piouffre, L., Bodmer, J. G., Bodmer, W. F., Bonné, B., Cambon‐Thomsen, A., et al. (2002) · Science · doi:10.1126/science.296.5566.261b · Cited by 997
A Mutation in VPS35, Encoding a Subunit of the Retromer Complex, Causes Late-Onset Parkinson Disease
Zimprich, A., Benet-Pagès, A., Struhal, W., Graf, E., Eck, S. H., Offman, M. N., Haubenberger, D., Spielberger, S., Schulte, E. C., Lichtner, P., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.06.008 · Cited by 816
VPS35 mutations in Parkinson disease
Vilariño-Güell, C., Wider, C., Ross, O. A., Dachsel, J. C., Kachergus, J. M., Lincoln, S. J., Soto-Ortolaza, A. I., Cobb, S. A., Wilhoite, G. J., Bacon, J. A., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.06.001 · Cited by 800
Whole-Genome Sequencing in a Patient with Charcot–Marie–Tooth Neuropathy
Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0908094 · Cited by 759
TREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342259 · Cited by 683
The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2
Klünemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000160304.00003.ca · Cited by 254
CNS manifestations of Nasu–Hakola disease
Bm, J., Autti, T., Raininko, R., Partanen, J., Salonen, O., Puranen, M., Hakola, P., & Haltia, M. (2001) · Neurology · doi:10.1212/wnl.56.11.1552 · Cited by 205
Bianchin, M. M., Capella, H. M., Chaves, D. L., Steindel, M., Grisard, E. C., Ganev, G. G., da Silva, J. P., Neto, E. S., Poffo, M. A., Walz, R., et al. (2004) · Cellular and Molecular Neurobiology · doi:10.1023/b:cemn.0000012721.08168.ee · Cited by 154
Mutations inTREM2lead to pure early-onset dementia without bone cysts
Chouery, É., Delague, V., Bergougnoux, A., Koussa, S., Serre, J., & Mégarbané, A. (2008) · Human Mutation · doi:10.1002/humu.20836 · Cited by 121
FancyGene: dynamic visualization of gene structures and protein domain architectures on genomic loci
Rambaldi, D., & Ciccarelli, F. D. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp381 · Cited by 99
An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene
Soragna, D. (2003) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.6.825-a · Cited by 75
Montalbetti, L., Ratti, M. T., Greco, B., APRILE, C., Moglia, A., & Soragna, D. (2005) · PubMed · Cited by 40
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“T66M mutation has also been identified to cause FTD-like syndrome.(344) Recently, Xie et al.”
Background
Metadata
- Authors
- Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., Emre, M., Singleton, A., & Hardy, J.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2013-01-01
- Volume
- 70
- Issue
- 1
- Pages
- 78
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4001789
- OpenAlex
- W1984557585
- Cited by
- 374
- References
- 27
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 20 · 2023: 17 · 2022: 12 · 2021: 39 · 2020: 34 · 2019: 22 · 2018: 32 · 2017: 37 · 2016: 29 · 2015: 40 · 2014: 26 · 2013: 21
- FWCI
- 27.37
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (089698)
- National Institutes of Health
- National Institute on Aging (Z01AG000950)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- TREM2, frontotemporal dementia, homozygous mutation, genetic diagnosis, white matter abnormalities, behavior change, cognitive impairment, exome sequencing, Turkish patients
- MeSH terms
- Adult, Humans, Male, Membrane Glycoproteins, Mutation, Receptors, Immunologic, Risk Factors, Syndrome, Frontotemporal Dementia, Exome
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