A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature

  title={A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature},
  author={Efthimios Dardiotis and Vasileios Siokas and Eva Pantazi and Maria Dardioti and Dimitrios Rikos and Georgia Xiromerisiou and Aikaterini Markou and Dimitra Papadimitriou and Matthaios Speletas and Georgios M. Hadjigeorgiou},
  journal={Neurobiology of Aging},

TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders.

The results expand the spectrum of neurodegenerative diseases, where the carriers of biallelic mutations in TREM2 have been described for Alzheimer's disease, and highlight the impact of variant burden in other genes on phenotypic heterogeneity.

Behavioral Variant Frontotemporal Dementia-like Syndrome With Novel Heterozygous TREM2 Frameshift Mutation.

A patient with a bvFTD-like syndrome is presented with compound heterozygosity for a previously recognized TREM2 missense mutation and a novel T REM2 frameshift mutation.

Phenotypic Expansion in Nasu-Hakola Disease: Immunological Findings in Three Patients and Proposal of a Unifying Pathogenic Hypothesis

Findings tend to redefine NHD as a multisystem “immunological” disease, considering that osteoclasts are derived from the fusion of mononuclear myeloid precursors, whereas neurological anomalies in NHD are directly caused by microglia dysfunction.

Frontotemporal Dementia and Chorea Associated with a Compound Heterozygous TREM2 Mutation.

A wide-range genetic analysis is performed, using a next generation sequencing approach, to evaluate a number of genes involved in neurodegeneration and found a previously unreported compound heterozygous mutation in TREM2, that is commonly associated with the recessively inherited Nasu-Hakola disease.

TREM2 variants in neurodegenerative disorders in the Polish population. Homozygosity and compound heterozygosity in FTD patients

Evaluating exon 2 of TREM2 gene variants as a putative genetic risk factor for Alzheimer’s disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) in the Polish population confirmed previous data that homozygous and compound heterozygous TREM1 mutations can be causative for FTD.

The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics

  • H. LokJ. Kwok
  • Biology, Psychology
    International journal of molecular sciences
  • 2021
The role of common variants and mutations in genes such as CSF1R (colony-stimulating factor 1 receptor), CYP27A1 (cytochrome P450 family 27 subfamily A member 1), TREM2 (triggering receptor expressed on myeloid cells 2) and TMEM106B (transmembrane protein 106B) that play an integral role in microglia and oligodendrocyte function are highlighted.

TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features

A combination of white matter changes, enlarged ventricles, atrophy of caudate nuclei, thinning of the corpus callosum in MRI strongly suggests NHD in patients with FTD syndrome.

Mechanistic insights into the deleterious roles of Nasu-Hakola disease associated TREM2 variants

Dynamical scenarios, as provided by the present study, may be critical to the understanding of the roles of these TREM2 mutations in neurodegenerative diseases.



An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene

The clinical and genetic analysis of an Italian family in which two siblings are affected by PLOSL is reported, and a homozygous mutation in the splice donor consensus site at intron 3 of TREM2 has been identified in two affected siblings.

Heterozygous TREM2 mutations in frontotemporal dementia

The genetic causes of basal ganglia calcification, dementia, and bone cysts

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy should be considered in adult patients under age 50 years with dementia and basal ganglia calcification.

Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement.

The results show that TREM2 is responsible for an unexpectedly high number of dementia cases in this cohort, suggesting that this gene should be taken into account when mutations in other dementia genes are excluded.

Mutations in TREM2 lead to pure early‐onset dementia without bone cysts

A genome‐wide screen using 382 STR markers to localize and identify the gene implicated in early‐onset dementia (EOD) without bone cysts in a Lebanese family with three affected subjects revealed a novel deletion in the 5' consensus donor splice site in intron 1 of TREM2, the first report of mutations in T REM2 causing a pure dementia.

CNS manifestations of Nasu–Hakola disease

Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations, suggesting patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists.

TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis.

This study demonstrates that the TREM2 p.R47H variant was more common in patients with ALS than in the controls and is therefore a significant risk factor for ALS, and highlights the T REM2 signaling pathway as a therapeutic target in ALS and other neurodegenerative diseases.