Home › Research › TREM2 and immune genetics
Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype
Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T et al.. American journal of human genetics, 2002-06-21
Topic: Brain proteins, microglia and lab models
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as "Nasu-Hakola disease," is a globally distributed recessively inherited disease leading to death during the 5th decade of life and is characterized by early-onset progressive dementia and bone cysts. Elsewhere, we have identified PLOSL mutations in TYROBP (DAP12), which codes for a membrane receptor component in natural-killer and myeloid cells, and also have identified genetic heterogeneity in PLOSL, with some patients carrying no mutations in TYROBP. Here we complete the molecular pathology of PLOSL by identifying TREM2 as the second PLOSL gene.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., et al. (2002). Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. American journal of human genetics. https://doi.org/10.1086/342259
Vancouver
Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. American journal of human genetics. 2002. doi:10.1086/342259. PMID: 12080485.
BibTeX
@article{paloneva2002-12080485,
author = {Paloneva, J. and Manninen, T. and Christman, G. and Hovanes, K. and Mandelin, J. and Adolfsson, R. and Bianchin, M. and Bird, T. and others},
title = {{Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype}},
journal = {American journal of human genetics},
year = {2002},
doi = {10.1086/342259},
pmid = {12080485},
url = {https://doi.org/10.1086/342259}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Elsewhere, we have identified PLOSL mutations in TYROBP (DAP12), which codes for a membrane receptor component in natural-killer and myeloid cells, and also have identified genetic heterogeneity in PLOSL, with some patients carrying no mutations in TYROBP.
- Here we complete the molecular pathology of PLOSL by identifying TREM2 as the second PLOSL gene.
- TREM2 forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells.
- Patients with PLOSL have no defects in cell-mediated immunity, suggesting a remarkable capacity of the human immune system to compensate for the inactive TYROBP-mediated activation pathway.
Why it matters
This 2002 study identified TREM2 as the second gene behind Nasu-Hakola disease (PLOSL), a recessively inherited condition with bone cysts and early-onset progressive dementia, in patients who had no mutations in the first known gene, TYROBP. Because TREM2 and TYROBP form one receptor signalling complex on immune cells, the authors conclude that faults in either part produce the same disease. It does not study Alzheimer's disease or test any treatment, and the record does not report how many patients were studied.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 53/100
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 (American journal of human genetics) |
| Journal's citation record | 3 / 4 | The American Journal of Human Genetics: journal h-index 385 (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 | 2002 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 684 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.3 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 3 / 6 | Cited 6.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 139 other studies in this library |
| Still being cited | 3 / 4 | Cited 84 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Leena Peltonen: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12080485) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1086/342259
- PubMed: 12080485
- Original source →
- Free full text: The American Journal of Human Genetics →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
139 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in TREM2 and immune genetics
Also in TREM2 and immune genetics
79 studies in the library are filed under TREM2 and immune genetics with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The TREM2 and immune genetics hub.