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Mutations in TREM2 lead to pure early-onset dementia without bone cysts
Chouery E, Delague V, Bergougnoux A, Koussa S, Serre JL, Mégarbané A.. Human mutation, 2008-09-01
Topic: Brain proteins, microglia and lab models
A genome-wide screen using 382 STR markers to localize and identify the gene implicated in early-onset dementia (EOD) without bone cysts in a Lebanese family with three affected subjects was conducted. A unique locus homozygous by descent at chromosome 6p21.2 locus was identified. Candidate genes were explored by fluorescent sequencing and the effect of the identified mutation was confirmed by qualitative and quantitative RT-PCR.
Key findings
- A unique locus homozygous by descent at chromosome 6p21.2 locus was identified.
- Candidate genes were explored by fluorescent sequencing and the effect of the identified mutation was confirmed by qualitative and quantitative RT-PCR.
- The genetic analysis revealed a novel deletion, c.40+3delAGG, in the 5' consensus donor splice site in intron 1 of TREM2 gene which is known to be responsible for PLOSL (Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy) also designated as Nasu-Hakola disease.
- In silico analysis predicted a lower strength for the novel donor splice site.
Why it matters
In a Lebanese family with three members affected by early-onset dementia but no bone cysts, a genome-wide search pointed to one region on chromosome 6, where the researchers found a new small deletion at a splicing signal in the TREM2 gene. TREM2 was already known to cause Nasu-Hakola disease (PLOSL), which includes bone cysts, so this study links the same gene to dementia without bone disease; a computer prediction suggested the mutated splice site is weaker, and the authors report confirming its effect with RNA tests. This comes from one family, does not concern common late-onset Alzheimer's disease, and does not show any treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Human mutation) |
| Journal's citation record | 2 / 4 | Human Mutation: journal h-index 219 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 124 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.2 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 38 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author André Mégarbané: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18546367) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Chouery, E., Delague, V., Bergougnoux, A., Koussa, S., Serre, J. L., & Mégarbané, A. (2008). Mutations in TREM2 lead to pure early-onset dementia without bone cysts. Human mutation. https://doi.org/10.1002/humu.20836
Vancouver
Chouery E, Delague V, Bergougnoux A, Koussa S, Serre JL, Mégarbané A. Mutations in TREM2 lead to pure early-onset dementia without bone cysts. Human mutation. 2008. doi:10.1002/humu.20836. PMID: 18546367.
BibTeX
@article{chouery2008-18546367,
author = {Chouery, E. and Delague, V. and Bergougnoux, A. and Koussa, S. and Serre, J. L. and Mégarbané, A.},
title = {{Mutations in TREM2 lead to pure early-onset dementia without bone cysts}},
journal = {Human mutation},
year = {2008},
doi = {10.1002/humu.20836},
pmid = {18546367},
url = {https://doi.org/10.1002/humu.20836}
}
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