title: Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy--PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects.
abstract: The authors review the clinical, radiological, electrophysiological, pathological, and molecular aspects of Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy or PLOSL). Nasu-Hakola disease is a unique disease characterized by multiple bone cysts associated with a peculiar form of neurodegeneration that leads to dementia and precocious death usually during the fifth decade of life. The diagnosis can be established on the basis of clinical and radiological findings. Recently, molecular analysis of affected families revealed mutations in the DAP12 (TYROBP) or TREM2 genes, providing an interesting example how mutations in two different subunits of a multi-subunit receptor complex result in an identical human disease phenotype. The association of PLOSL with mutations in the DAP12 or TREM2 genes has led to improved diagnosis of affected individuals. Also, the possible roles of the DAP12/TREM2 signaling pathway in microglia and osteoclasts in humans are just beginning to be elucidated. Some aspects of this peculiar signaling pathway are discussed here.
authors.affiliation: CIREP, Department of Neurology, Psychiatry and Medical Psychology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil. mmbianchin@rnp.fmrp.usp.br
authors.forename: Marino Muxfeldt
authors.initials: MM
authors.lastname: Bianchin
authors.forename: Heraldo M
authors.initials: HM
authors.lastname: Capella
authors.forename: Daniel Loureiro
authors.initials: DL
authors.lastname: Chaves
authors.forename: Mário
authors.initials: M
authors.lastname: Steindel
authors.forename: Edmundo C
authors.initials: EC
authors.lastname: Grisard
authors.forename: Gerson Gandi
authors.initials: GG
authors.lastname: Ganev
authors.forename: João Péricles
authors.initials: JP
authors.lastname: da Silva Júnior
authors.forename: Schaeffer
authors.initials: S
authors.lastname: Neto Evaldo
authors.forename: Mônica Aparecida
authors.initials: MA
authors.lastname: Poffo
authors.forename: Roger
authors.initials: R
authors.lastname: Walz
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Carlotti Júnior
authors.forename: Américo C
authors.initials: AC
authors.lastname: Sakamoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001847:Bone Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D015140:Dementia, Vascular / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017628:Microglia / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010006:Osteoblasts / Q000378:metabolism; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C498715:TREM2 protein, human; C110546:TYROBP protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1