An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene
Open accessAbstract
Polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disorder characterised by systemic bone cysts and progressive presenile dementia associated with sclerosing leucoencephalopathy.1 The onset usually occurs in the third decade of life with pathological fractures; later on, symptoms of frontal lobe dysfunction appear, with upper motor neurone involvement and epileptic seizures. Some patients, however, do not have clinically manifest osseous problems despite the radiological demonstration of cystic bone lesions. The disease leads to death before the age of 50.1 The disease is characterised by genetic heterogeneity: mutations in two genes (TYROBP and TREM2) encoding different subunits of a membrane receptor complex in natural killer and myeloid cells have been associated with the disease.2,3 This rare disorder was initially described in Finland and Japan but is now recognised to have a worldwide distribution.1 In particular, sporadic cases have been described in Italy,4,5 and a homozygous mutation in the splice donor consensus site at intron 3 of TREM2 has been identified in two affected siblings.3 We report here the clinical and genetic analysis of an Italian family in which two siblings are affected by PLOSL. After giving …
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AD-associated TREM2 risk variants - including p.H157Y, p.R98W, p.D87N, p.T66M, p.R62H, p.R47H, p.Y38C and p.Q33X - affect TREM2 function by various mechanisms.
“AD-associated TREM2 risk variants – including p.H157Y, p.R98W, p.D87N, p.T66M, p.R62H, p.R47H, p.Y38C and p.Q33X [6, 43] – affect TREM2 function by various mechanisms”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [43]
TREM2 p.Q33X causes loss of TREM2 expression.
“Loss of TREM2 expression [43]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [43]
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- Authors
- Soragna, D.
- Affiliations
- University of Pavia (IT)
- Corresponding author
- Soragna, D
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2003-06-01
- Volume
- 74
- Issue
- 6
- Pages
- 825-a-826
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC1738498
- OpenAlex
- W1975504757
- Cited by
- 75
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 10 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 4
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- National Institutes of Health (RR-00052)
- U.S. Public Health Service
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Nasu-Hakola disease, TREM2, novel mutations, TYROBP, bone cysts, early-onset dementia, familial inheritance, Italian families
- MeSH terms
- Triggering Receptor Expressed on Myeloid Cells-1, Adult, Bone Cysts, Dementia, DNA Mutational Analysis, Female, Humans, Membrane Glycoproteins, Membrane Proteins, Middle Aged, Terminology as Topic, Pedigree, Proteins, Receptors, Immunologic, Subacute Sclerosing Panencephalitis, Point Mutation, Adaptor Proteins, Signal Transducing
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