Cited by 462Genomics and Rare DiseasesBone Metabolism and DiseasesGenetics and Neurodevelopmental Disorders

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Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts

Paloneva, Juha, Kestilä, Marjo, Wu, Jun, Salminen, Antti, Böhling, Tom, Ruotsalainen, Vesa, Hakola, Panu, Bakker, Alexander B.H., Phillips, Joseph H., Pekkarinen, Petra, Lanier, Lewis L., Timonen, Tuomo, Peltonen, Leena·2000·Nature Genetics

DOI 10.1038/77153

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Abstract

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.

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Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684
Prediction of complete gene structures in human genomic DNA
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Self-citation
An activating immunoreceptor complex formed by NKG2D and DAP10.
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Self-citation
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Peltonen, L. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.10.1913 · Cited by 488
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The origin and differentiation of microglial cells during development
Cuadros, M. Á. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00035-5 · Cited by 305

Show all 31 references

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Hakola, H.P.A. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy). A neuropsychiatric follow-up study. (monograph 17) in Monographs of Psychiatria Fennica (eds Henriksson, M., Huttunen, M., Kuoppasalmi, K., Lindfors, O. & Lönnqvist, J.) 1–114 (Foundation for Psychiatric Research in Finland, Helsinki, 1990).

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Authors: Paloneva, J., Kestilä, M., Wu, J., Salminen, A., Böhling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B. H., Phillips, J. H., Pekkarinen, P., Lanier, L. L., Timonen, T., & Peltonen, L.
Affiliations: University of Helsinki (FI)
University of California, San Francisco (US)
University of Oulu (FI)
University of Eastern Finland (FI)
University of California, Los Angeles (US)
Corresponding author: Peltonen, Leena
ORCID: Paloneva, Juha
Salminen, Antti
Böhling, Tom
Lanier, Lewis L.
Peltonen, Leena
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2000-07
Volume: 25
Issue: 3
Pages: 357-361
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/77153
OpenAlex: W1607556721
Cited by: 460
References: 31
Citations by year: 2026: 12 · 2025: 10 · 2024: 17 · 2023: 16 · 2022: 18 · 2021: 23 · 2020: 19 · 2019: 16 · 2018: 24 · 2017: 25 · 2016: 21 · 2015: 28 · 2014: 21 · 2013: 20 · 2012: 15
FWCI: 9.17
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: Nasu-Hakola disease, TYROBP, DAP12, loss-of-function mutations, early-onset dementia, bone cysts, chromosome 19q13.1, NK cell signaling, natural killer cells, MHC class I recognition
MeSH terms: Adult, Alzheimer Disease, Amino Acid Sequence, Base Sequence, Bone Cysts, Finland, Humans, Japan, Killer Cells, Natural, Membrane Proteins, Middle Aged, Molecular Sequence Data, Receptors, Immunologic, Mutagenesis, Sequence Deletion, DNA, Complementary, Adaptor Proteins, Signal Transducing

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Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts

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