title: A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature.
abstract: Nasu-hakola disease (NHD) is a rare disease characterized by bone cysts and fractures, frontal lobe syndrome, and progressive presenile dementia. NHD may be the prototype of primary microglial disorders of the CNS or, as they have been coined, "microgliopathies". Mutations in TREM2 and TYROBP genes are known to cause NHD. Interestingly, recent evidence-associated rare genetic variants of TREM2 gene with increased risk of Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Parkinson's disease. Here, we report a 33-year-old Greek female with phenotype suggestive of NHD. Full gene sequencing of the TREM2 and TYROBP genes revealed a novel mutation in exon 2 of TREM2 gene, namely c.244G>T (p.W50C) and heterozygosity in the parents and her brother. This report extends the range of TREM2 mutations that cause NHD phenotype. In addition, we provide a comprehensive review of all reported in the literature TREM2 gene mutations and the respective wide spectrum of clinical manifestations that highlights the importance of considering TREM2 gene mutations in a variety of neurodegenerative phenotypes.
authors.affiliation: Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece; Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Efthimios
authors.initials: E
authors.lastname: Dardiotis
authors.affiliation: Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Siokas
authors.affiliation: Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Eva
authors.initials: E
authors.lastname: Pantazi
authors.affiliation: Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Dardioti
authors.affiliation: Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Rikos
authors.affiliation: Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Xiromerisiou
authors.affiliation: Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Markou
authors.affiliation: Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.affiliation: Department of Immunology and Histocompatibility, School of Health Sciences, Faculty of Medicine, University of Thessaly, Biopolis, Larissa, Greece.
authors.forename: Matthaios
authors.initials: M
authors.lastname: Speletas
authors.affiliation: Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece; Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece. Electronic address: gmhadji@med.uth.gr.
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008060:Lipodystrophy / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics*; D013344:Subacute Sclerosing Panencephalitis / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; C110546:TYROBP protein, human
keywords: Microgliopathies; Nasu-hakola disease; Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; TREM2 gene mutations