PLOSL1
MCID: PLY180
MIFTS: 56

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 (PLOSL1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

MalaCards integrated aliases for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

Name: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 56 73 29 6
Nasu-Hakola Disease 56 12 24 52 25 58 73 36 29 13 54 15
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 12 24 52 25 58 29 43 39
Nhd 56 12 52 25 58 73
Presenile Dementia with Bone Cysts 56 12 52 25 73
Plosl 56 12 52 25 58
Plo-Sl 12 25 58
Dementia, Progressive, with Lipomembranous Polycystic Osteodysplasia 56 52
Dementia, Prefrontal, with Bone Cysts 56 52
Brain-Bone-Fat Disease 56 52
Plosl1 56 73
Progressive Dementia with Lipomembranous Polycystic Osteodysplasia; Brain-Bone-Fat Disease 12
Nasu-Hakola Disease; Nhd 56

Characteristics:

Orphanet epidemiological data:

58
nasu-hakola disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Finland); Age of onset: Adolescent,Adult; Age of death: adult;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
profound dementia and death usually occurs by age 50 years


HPO:

31
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2770 Definition Nasu-Hakola disease (NHD), also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities. Epidemiology Over 200 cases have been reported worldwide in the literature, the majority of them being in the Japanese and Finnish population. The prevalence in Finland is estimated between 1/500,000 and 1/1,000,000. Clinical description The disease course is generally divided into four stages: latent, osseous, early neurologic, and late neurologic. After a normal development during childhood (latent stage), the disease starts manifesting during adolescence or young adulthood (typical age of onset 20-30 years) with pain in the hands, wrists, ankles, and feet. Patients then start suffering from recurrent bone fractures due to polycystic osseous and osteoporotic lesions in the limb bones (osseous stage). During the third or fourth decade of life (early neurologic stage), patients present with pronounced personality changes (e.g. euphoria, lack of concentration, loss of judgment and social inhibitions) characteristic of a frontal lobe syndrome . Patients also typically suffer from initially mild, but progressive, memory disturbances. Epileptic seizures are frequently observed. Finally (late neurologic stage), patients progress to a profound dementia, are unable to speak and move, and usually die by the age of 50 years. Occasionally, the disease presents a different course with the neurologic symptoms preceding the osseous ones. Etiology NHD is due to mutations in either the TYROBP or TREM2 genes encoding the tyrosine kinase binding adaptor protein and the triggering receptor expressed on myeloid cells 2 respectively. These genes encode components of a signaling complex involved in the regulation of immune responses, the differentiation of dendritic cells and osteoclasts, and in the phagocytic activity of microglia. The exact pathogenic mechanism is unknown. Diagnostic methods Diagnosis is based on clinical and radiologic examination. X-ray imaging shows multifocal cystic lesions on the bones of hands, wrists, feet and ankles. Brain computed tomography (CT) or magnetic resonance imaging (MRI) shows frontally accentuated atrophy of the cerebral white matter. Bilateral calcifications of the basal ganglia are typical. EEG is normal in the early stages but shows diffuse slowing and irritative activity in late stages. Histopathologically, loss of axons and myelin as well as fibrillary gliosis are observed. Molecular genetic testing confirms the diagnosis in ambiguous cases. Differential diagnosis The combination of frontal-type dementia starting in the fourth decade and radiologically demonstrable polycystic osseous lesions is unique and facilitates the differentiation of NHD from other forms of familial and non-familial frontotemporal dementia such as frontotemporal dementia and parkinsonism linked to chromosome 17 (see this term). Antenatal diagnosis Due to the low carrier frequency of the mutation in the general population, prenatal diagnostic procedures are usually not reasonable, except in genetic isolates. Genetic counseling Transmission is autosomal recessive . Children of an NHD patient are healthy carriers of the mutation unless they have also inherited a disease-causing mutation in the TYROBP or TREM2 genes from the other parent. Presymptomatic testing is commercially available. Management and treatment There is no curative treatment for the disease. Management is supportive. Antiepileptic drugs are prescribed to prevent seizures. A regular orthopedic and neurologic surveillance is recommended. Prognosis NHD is a progressive disease that is fatal usually during the fifth decade of life. Visit the Orphanet disease page for more resources.

MalaCards based summary : Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1, also known as nasu-hakola disease, is related to dementia and solitary bone cyst, and has symptoms including seizures, myoclonus and personality changes. An important gene associated with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 is TYROBP (Transmembrane Immune Signaling Adaptor TYROBP), and among its related pathways/superpathways are Osteoclast differentiation and Innate Immune System. Affiliated tissues include bone, brain and myeloid, and related phenotypes are skeletal dysplasia and developmental regression

Disease Ontology : 12 A syndrome that is characterized by progressive presenile dementia and recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities that has material basis in homozygous mutation in the TYRO protein tyrosine kinase binding protein (TYROBP) gene on chromosome 19q13 or homozygous mutation in the triggering receptor expressed on myeloid cells 2 (TREM2) gene on chromosome 6p21.

Genetics Home Reference : 25 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, commonly known as PLOSL, is a progressive disorder that affects the bones and brain. "Polycystic lipomembranous osteodysplasia" refers to cyst-like bone changes that can be seen on x-rays. "Sclerosing leukoencephalopathy" describes specific changes in the brain that are found in people with this disorder. The bone abnormalities associated with PLOSL usually become apparent in a person's twenties. In most affected individuals, pain and tenderness in the ankles and feet are the first symptoms of the disease. Several years later, broken bones (fractures) begin to occur frequently, particularly in bones of the ankles, feet, wrists, and hands. Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cyst-like changes. These abnormalities weaken bones and make them more likely to break. The brain abnormalities characteristic of PLOSL typically appear in a person's thirties. Personality changes are among the first noticeable problems, followed by a loss of judgment, feelings of intense happiness (euphoria), a loss of inhibition, and poor concentration. These neurologic changes cause significant problems in an affected person's social and family life. As the disease progresses, it causes a severe decline in thinking and reasoning abilities (dementia). Affected people ultimately become unable to walk, speak, or care for themselves. People with this disease usually live only into their thirties or forties.

OMIM : 56 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usuallly leads to death in the fifth decade of life (summary by Kondo et al., 2002). (221770)

KEGG : 36 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-hakola disease is an autosomal recessive inherited disorder. It is characterized by repeated fractures occurring during adolescence and progressive presenile dementia in the fourth decade. The disease is caused by a mutation in the TREM2 or DAP12 gene that regulates osteoclast differentiation. TREM2-DAP12 is also expressed by microglia, thus neurological impairments seen in this disease are considered to be directly caused by microglial dysfunstion.

UniProtKB/Swiss-Prot : 73 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1: A recessively inherited disease characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usuallly leads to death in the fifth decade of life.

Wikipedia : 74 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease... more...

GeneReviews: NBK1197

Related Diseases for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Diseases in the Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 family:

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2

Diseases related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 51)
# Related Disease Score Top Affiliating Genes
1 dementia 30.8 TYROBP TREM2 CSF1R APOE
2 solitary bone cyst 30.8 TYROBP TREM2
3 polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 11.9
4 osteoarthritis with mild chondrodysplasia 11.5
5 autosomal recessive disease 11.0
6 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 10.8
7 alzheimer disease 10.6
8 amyotrophic lateral sclerosis 1 10.5
9 frontotemporal dementia 10.5
10 leukodystrophy 10.5
11 lateral sclerosis 10.5
12 alcohol dependence 10.5
13 hydrocephalus 10.5
14 brain edema 10.5
15 creutzfeldt-jakob disease 10.3
16 basal ganglia calcification, idiopathic, 1 10.3
17 metachromatic leukodystrophy 10.3
18 myoclonic epilepsy of unverricht and lundborg 10.3
19 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.3
20 basal ganglia calcification 10.3
21 bone disease 10.3
22 bone resorption disease 10.3
23 hypoparathyroidism 10.3
24 status epilepticus 10.3
25 neuroaxonal dystrophy 10.3
26 acute kidney failure 10.3
27 early myoclonic encephalopathy 10.3
28 lysosomal storage disease 10.3
29 peripheral nervous system disease 10.3
30 paraplegia 10.3
31 prion disease 10.3
32 neuropathy 10.3
33 myotonic dystrophy 10.3
34 cerebral atrophy 10.3
35 persistent vegetative state 10.3
36 tremor 10.3
37 semantic dementia 10.3 TREM2 APOE
38 allergic rhinitis 10.2
39 hyperlipoproteinemia, type iii 10.2
40 lipoprotein quantitative trait locus 10.2
41 rhinitis 10.2
42 leukoencephalopathy, hereditary diffuse, with spheroids 10.2 TYROBP TREM2 IL34 CSF1R
43 tenosynovial giant cell tumor 10.2 IL34 CSF1R
44 kohlschutter-tonz syndrome 10.2
45 langerhans cell histiocytosis 10.2
46 demyelinating disease 10.2
47 histiocytosis 10.2
48 hemangioendothelioma 10.2
49 skeletal-extraskeletal angiomatosis 10.2
50 angiomatosis 10.2

Graphical network of the top 20 diseases related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:



Diseases related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1

Symptoms & Phenotypes for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Human phenotypes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

58 31 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
2 developmental regression 58 31 hallmark (90%) Very frequent (99-80%) HP:0002376
3 irritability 58 31 hallmark (90%) Very frequent (99-80%) HP:0000737
4 arthralgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002829
5 reduced bone mineral density 58 31 hallmark (90%) Very frequent (99-80%) HP:0004349
6 memory impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0002354
7 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
8 ventriculomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002119
9 abnormality of epiphysis morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0005930
10 limitation of joint mobility 58 31 hallmark (90%) Very frequent (99-80%) HP:0001376
11 bone cyst 58 31 hallmark (90%) Very frequent (99-80%) HP:0012062
12 bone pain 58 31 hallmark (90%) Very frequent (99-80%) HP:0002653
13 disinhibition 58 31 hallmark (90%) Very frequent (99-80%) HP:0000734
14 abnormal adipose tissue morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0009124
15 personality changes 58 31 hallmark (90%) Very frequent (99-80%) HP:0000751
16 frontal lobe dementia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000727
17 neurological speech impairment 58 31 frequent (33%) Frequent (79-30%) HP:0002167
18 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
19 chorea 58 31 frequent (33%) Frequent (79-30%) HP:0002072
20 cerebral calcification 58 31 frequent (33%) Frequent (79-30%) HP:0002514
21 oculomotor apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0000657
22 agnosia 58 31 frequent (33%) Frequent (79-30%) HP:0010524
23 seizure 31 frequent (33%) HP:0001250
24 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000238
25 acute leukemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002488
26 functional abnormality of the gastrointestinal tract 58 31 occasional (7.5%) Occasional (29-5%) HP:0012719
27 behavioral abnormality 58 Very frequent (99-80%)
28 seizures 58 Frequent (79-30%)
29 eeg abnormality 31 HP:0002353
30 gait disturbance 31 HP:0001288
31 myoclonus 31 HP:0001336
32 abnormality of movement 58 Frequent (79-30%)
33 abnormality of the foot 31 HP:0001760
34 babinski sign 31 HP:0003487
35 hypoplasia of the corpus callosum 31 HP:0002079
36 leukoencephalopathy 31 HP:0002352
37 cerebral atrophy 31 HP:0002059
38 aggressive behavior 31 HP:0000718
39 abnormality of the hand 31 HP:0001155
40 urinary incontinence 31 HP:0000020
41 pathologic fracture 31 HP:0002756
42 apraxia 31 HP:0002186
43 abnormal upper motor neuron morphology 31 HP:0002127
44 gliosis 31 HP:0002171
45 inappropriate behavior 31 HP:0000719
46 lack of insight 31 HP:0000757
47 peripheral demyelination 31 HP:0011096
48 axonal loss 31 HP:0003447
49 primitive reflex 31 HP:0002476
50 caudate atrophy 31 HP:0002340

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
gait disturbance
spasticity
myoclonus
cerebral atrophy
more
Genitourinary Bladder:
urinary incontinence

Skeletal Hands:
bone cysts in phalangeal, metacarpal, and carpal bones

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior
disinhibition
personality changes
frontal lobe dementia
inappropriate behavior
more
Skeletal Limbs:
pathologic fractures
pain and swelling in ankles and wrists after stress or injury beginning around age 20 years
bone cysts filled with necrotic, fatty material
cysts in patella and ends of long bones

Skeletal Feet:
bone cysts in phalangeal, metatarsal, and tarsal bones

Clinical features from OMIM:

221770

UMLS symptoms related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:


seizures, myoclonus, personality changes, muscle spasticity, upper motor neuron signs

MGI Mouse Phenotypes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.9 APOE CSF1R CX3CR1 HCST IL34 SDHD
2 immune system MP:0005387 9.7 APOE CLEC5A CSF1R CX3CR1 HCST IL34
3 no phenotypic analysis MP:0003012 9.17 APOE CSF1R CX3CR1 HCST IL34 SYK

Drugs & Therapeutics for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Search Clinical Trials , NIH Clinical Center for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1

Cochrane evidence based reviews: polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Genetic Tests for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Genetic tests related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

# Genetic test Affiliating Genes
1 Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 29 TYROBP
2 Nasu-Hakola Disease 29
3 Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (plosl) 29

Anatomical Context for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

MalaCards organs/tissues related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

40
Bone, Brain, Myeloid, Testes, Monocytes, Nk Cells, Bone Marrow

Publications for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Articles related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

(show top 50) (show all 181)
# Title Authors PMID Year
1
Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. 6 56 54 24 61
10888890 2000
2
Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. 61 56 6 24
12370476 2002
3
The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. 56 24 61 54
15883308 2005
4
CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. 61 24 56
11402114 2001
5
Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13. 24 56
9463329 1998
6
Nasu-Hakola syndrome: polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy and presenile dementia. 24 56
9321763 1997
7
Vascular changes and blood-brain barrier damage in the pathogenesis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy). 56 24
8085433 1994
8
A novel compound heterozygous mutation in the DAP12 gene in a patient with Nasu-Hakola disease. 61 24 54
17125796 2007
9
DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. 24 54 61
12925681 2003
10
Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium. 56 54
9828133 1998
11
Coding variants in TREM2 increase risk for Alzheimer's disease. 61 24
24899047 2014
12
Homozygous TREM2 mutation in a family with atypical frontotemporal dementia. 24 61
24910390 2014
13
Membranous lipodystrophy: skeletal findings on CT and MRI. 24 61
24777445 2014
14
C9ORF72 expansion does not affect the phenotype in Nasu-Hakola disease with the DAP12 mutation. 61 24
24612676 2014
15
Extremity manifestations and surgical treatment for nasu hakola disease. 24 61
24711942 2014
16
Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family. 61 24
23870839 2013
17
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): a new report of an Italian woman and review of the literature. 24 61
23399524 2013
18
Gray matter lesions in Nasu-Hakola disease: a report on three autopsy cases. 24 61
20880319 2011
19
Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease. 24 61
18404378 2009
20
Mutations in TREM2 lead to pure early-onset dementia without bone cysts. 24 61
18546367 2008
21
Regional cerebral blood flow in a patient with Nasu-Hakola disease. 61 24
16097640 2005
22
Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. 24 61
15728241 2005
23
Impaired differentiation of osteoclasts in TREM-2-deficient individuals. 61 24
12913093 2003
24
An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene. 24 61
12754369 2003
25
Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. 61 24
12080485 2002
26
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) 6
20301376 2002
27
Hypothalamic haemorrhage and thalamus degeneration in a case of Nasu-Hakola disease with hallucinatory symptoms and central hypothermia. 24 61
10787346 2000
28
A case of membranous lipodystrophy (Nasu-Hakola disease) with unique MRI findings. 24 61
8570051 1995
29
Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: report of an autopsied case. 24 61
1722609 1991
30
Nasu-Hakola disease (membranous lipodystrophy). Clinical, histopathological and biochemical studies of three cases. 61 24
2746291 1989
31
Hereditary polycystic osteodysplasia with progressive dementia in Sweden. 56
77975 1978
32
Membranous lipodystrophy of bone. 56
579591 1978
33
Lipomembranous polycystic osteodysplasia. 56
827851 1976
34
Bone mineral content in hereditary polycystic osteodysplasia associated with progressive dementia. 56
1189965 1975
35
A new hereditary disease with progressive dementia and polycystic osteodysplasia: neuroradiological analysis of seven cases. 56
4764488 1973
36
TREM2 variants in Alzheimer's disease. 24
23150934 2013
37
Variant of TREM2 associated with the risk of Alzheimer's disease. 24
23150908 2013
38
Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. 24
23318515 2013
39
Word list learning in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. 24
23569454 2013
40
Rorschach assessment of personality functioning in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. 24
25286817 2012
41
TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. 54 61
20484116 2010
42
The surface-exposed chaperone, Hsp60, is an agonist of the microglial TREM2 receptor. 61 54
19457124 2009
43
DAP10- and DAP12-associated receptors in innate immunity. 24
19120482 2009
44
Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function. 54 61
18612411 2008
45
Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis. 54 61
17407101 2007
46
TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. 61 54
16418779 2006
47
Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. 24
16313340 2005
48
Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. 24
15686960 2005
49
The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. 24
14969392 2004
50
Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy--PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. 61 54
15049507 2004

Variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

ClinVar genetic disease variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TREM2 NM_018965.3(TREM2):c.97C>T (p.Gln33Ter)SNV Pathogenic 5219 rs104894002 6:41129295-41129295 6:41161557-41161557
2 TYROBP TYROBP, EX1-4DELdeletion Pathogenic 5795
3 TYROBP TYROBP, 1-BP DEL, 141Gdeletion Pathogenic 5796
4 TYROBP NM_003332.4(TYROBP):c.2T>C (p.Met1Thr)SNV Pathogenic 5797 rs104894732 19:36399129-36399129 19:35908227-35908227
5 TREM2 NM_018965.3(TREM2):c.197C>T (p.Thr66Met)SNV Pathogenic 192242 rs201258663 6:41129195-41129195 6:41161457-41161457
6 TREM2 NM_018965.3(TREM2):c.113A>G (p.Tyr38Cys)SNV Pathogenic 192241 rs797044603 6:41129279-41129279 6:41161541-41161541
7 TYROBP NG_009304.1:g.2160_7401deldeletion Pathogenic 192243 19:36396786-36402027 19:35905884-35911125
8 TREM2 NM_018965.3(TREM2):c.40G>T (p.Glu14Ter)SNV Pathogenic 56724 rs386834143 6:41130781-41130781 6:41163043-41163043
9 TYROBP NM_003332.4(TYROBP):c.141del (p.Met48fs)deletion Pathogenic/Likely pathogenic 56395 rs386833840 19:36398436-36398436 19:35907534-35907534
10 TREM2 NM_018965.4(TREM2):c.40+4_40+6deldeletion Pathogenic/Likely pathogenic 56723 rs386834142 6:41130775-41130777 6:41163037-41163039
11 TYROBP NM_003332.4(TYROBP):c.145G>C (p.Gly49Arg)SNV Likely pathogenic 56396 rs386833841 19:36398432-36398432 19:35907530-35907530
12 TYROBP NM_003332.4(TYROBP):c.262G>T (p.Glu88Ter)SNV Likely pathogenic 56397 rs386833842 19:36398134-36398134 19:35907232-35907232
13 TREM2 NM_018965.3(TREM2):c.269del (p.Gly90fs)deletion Likely pathogenic 56721 rs386834140 6:41129123-41129123 6:41161385-41161385
14 TREM2 NM_018965.3(TREM2):c.313del (p.Ala105fs)deletion Likely pathogenic 56722 rs386834141 6:41129079-41129079 6:41161341-41161341
15 TYROBP NM_003332.4(TYROBP):c.116G>A (p.Ser39Asn)SNV Likely pathogenic 56394 rs386833839 19:36398461-36398461 19:35907559-35907559
16 TREM2 NM_018965.3(TREM2):c.233G>A (p.Trp78Ter)SNV Likely pathogenic 5213 rs104893998 6:41129159-41129159 6:41161421-41161421
17 TREM2 NM_018965.3(TREM2):c.377T>G (p.Val126Gly)SNV Likely pathogenic 5218 rs121908402 6:41129015-41129015 6:41161277-41161277
18 TREM2 NM_018965.3(TREM2):c.482+2T>CSNV Likely pathogenic 56725 rs386834144 6:41127528-41127528 6:41159790-41159790
19 TREM2 NM_018965.3(TREM2):c.399G>T (p.Leu133=)SNV Conflicting interpretations of pathogenicity 290058 rs144250872 6:41127613-41127613 6:41159875-41159875
20 TREM2 NM_018965.3(TREM2):c.185G>A (p.Arg62His)SNV Conflicting interpretations of pathogenicity 445645 rs143332484 6:41129207-41129207 6:41161469-41161469
21 TYROBP NM_003332.4(TYROBP):c.46C>T (p.Leu16=)SNV Conflicting interpretations of pathogenicity 732760 19:36399085-36399085 19:35908183-35908183
22 TYROBP NM_003332.4(TYROBP):c.111G>A (p.Thr37=)SNV Conflicting interpretations of pathogenicity 737347 19:36398466-36398466 19:35907564-35907564
23 TYROBP NM_003332.4(TYROBP):c.*154T>CSNV Uncertain significance 890876 19:36395317-36395317 19:35904415-35904415
24 TYROBP NM_003332.4(TYROBP):c.180C>G (p.Ala60=)SNV Uncertain significance 892113 19:36398397-36398397 19:35907495-35907495
25 TYROBP NM_003332.4(TYROBP):c.140T>C (p.Val47Ala)SNV Uncertain significance 892114 19:36398437-36398437 19:35907535-35907535
26 TYROBP NM_003332.4(TYROBP):c.112G>A (p.Val38Met)SNV Uncertain significance 892115 19:36398465-36398465 19:35907563-35907563
27 TYROBP NM_003332.4(TYROBP):c.230-3C>TSNV Uncertain significance 892112 19:36398169-36398169 19:35907267-35907267
28 TYROBP NM_003332.4(TYROBP):c.*5G>ASNV Uncertain significance 328893 rs372703196 19:36395466-36395466 19:35904564-35904564
29 TYROBP NM_003332.4(TYROBP):c.-50G>ASNV Uncertain significance 328898 rs371441146 19:36399180-36399180 19:35908278-35908278
30 TYROBP NM_003332.4(TYROBP):c.*85C>TSNV Uncertain significance 328890 rs374144427 19:36395386-36395386 19:35904484-35904484
31 TYROBP NM_003332.4(TYROBP):c.-34C>TSNV Uncertain significance 328897 rs199931680 19:36399164-36399164 19:35908262-35908262
32 TYROBP NM_003332.4(TYROBP):c.*103T>ASNV Uncertain significance 328889 rs777094340 19:36395368-36395368 19:35904466-35904466
33 TREM2 NM_018965.3(TREM2):c.*111A>GSNV Uncertain significance 356673 rs753777378 6:41126391-41126391 6:41158653-41158653
34 TREM2 NM_018965.3(TREM2):c.514C>T (p.Pro172Ser)SNV Likely benign 522336 rs781302866 6:41126773-41126773 6:41159035-41159035
35 TREM2 NM_018965.3(TREM2):c.287C>A (p.Thr96Lys)SNV Benign/Likely benign 356678 rs2234253 6:41129105-41129105 6:41161367-41161367
36 TREM2 NM_018965.3(TREM2):c.632T>C (p.Leu211Pro)SNV Benign/Likely benign 356676 rs2234256 6:41126655-41126655 6:41158917-41158917
37 TYROBP NM_003332.4(TYROBP):c.*83C>TSNV Benign 328891 rs14715 19:36395388-36395388 19:35904486-35904486
38 TYROBP NM_003332.4(TYROBP):c.163G>T (p.Val55Leu)SNV Benign 196360 rs77782321 19:36398414-36398414 19:35907512-35907512
39 TYROBP NM_003332.4(TYROBP):c.*140T>CSNV Benign 328888 rs113207157 19:36395331-36395331 19:35904429-35904429
40 TYROBP NM_003332.4(TYROBP):c.*25A>CSNV Benign 328892 rs1802029 19:36395446-36395446 19:35904544-35904544
41 TYROBP NM_003332.4(TYROBP):c.123C>G (p.Gly41=)SNV Benign 328894 rs111477177 19:36398454-36398454 19:35907552-35907552
42 TYROBP NM_003332.3(TYROBP):c.94+10G>CSNV Benign 328895 rs55746266 19:36398622-36398622 19:35907720-35907720
43 TYROBP NM_003332.3(TYROBP):c.68G>A (p.Arg23His)SNV Benign 328896 rs79272253 19:36398658-36398658 19:35907756-35907756

Expression for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Search GEO for disease gene expression data for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1.

Pathways for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Pathways related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to KEGG:

36
# Name Kegg Source Accession
1 Osteoclast differentiation hsa04380

Pathways related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.53 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
2
Show member pathways
13.04 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
3 11.46 TYROBP TREM2 SYK SIRPB1 CSF1R
4 11.3 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1

GO Terms for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Cellular components related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.93 TYROBP TREML2 TREML1 TREM2 TREM1 TMEM119
2 plasma membrane GO:0005886 9.8 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
3 cell surface GO:0009986 9.28 TYROBP TREML4 TREML2 TREML1 SIRPB1 HCST

Biological processes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:

(show all 25)
# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 10.04 TYROBP TREML4 SYK IL34 CSF1R CLEC5A
2 positive regulation of protein phosphorylation GO:0001934 9.81 TREM2 TMEM119 IL34 CSF1R
3 response to ischemia GO:0002931 9.67 TREM2 CX3CR1 CSF1R
4 cellular defense response GO:0006968 9.63 TYROBP CX3CR1 CLEC5A
5 apoptotic cell clearance GO:0043277 9.62 TYROBP TREM2
6 positive regulation of tumor necrosis factor biosynthetic process GO:0042535 9.62 TYROBP SYK
7 positive regulation of superoxide anion generation GO:0032930 9.61 TYROBP SYK
8 positive regulation of macrophage chemotaxis GO:0010759 9.61 IL34 CSF1R
9 negative regulation of interleukin-1 beta production GO:0032691 9.6 TREM2 CX3CR1
10 positive regulation of calcium-mediated signaling GO:0050850 9.59 TREM2 SYK
11 positive regulation of interleukin-6 biosynthetic process GO:0045410 9.58 TYROBP SYK
12 macrophage activation involved in immune response GO:0002281 9.58 TYROBP SYK
13 positive regulation by host of viral process GO:0044794 9.56 CSF1R APOE
14 positive regulation of microglial cell migration GO:1904141 9.55 TREM2 CX3CR1
15 positive regulation of amyloid-beta clearance GO:1900223 9.54 TREM2 APOE
16 osteoclast differentiation GO:0030316 9.54 TYROBP TREM2 CSF1R
17 positive regulation of macrophage proliferation GO:0120041 9.52 IL34 CSF1R
18 negative regulation of long-term synaptic potentiation GO:1900272 9.5 TYROBP CX3CR1 APOE
19 regulation of immune response GO:0050776 9.5 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
20 neutrophil activation involved in immune response GO:0002283 9.48 TYROBP SYK
21 regulation of innate immune response GO:0045088 9.46 TREML4 TREML2 TREM2 APOE
22 positive regulation of macrophage fusion GO:0034241 9.43 TYROBP TREM2
23 microglial cell proliferation GO:0061518 9.43 TREM2 IL34 CSF1R
24 microglial cell activation involved in immune response GO:0002282 9.4 TYROBP TREM2
25 innate immune response GO:0045087 9.36 TYROBP TREML4 TREML1 TREM2 TREM1 SYK

Molecular functions related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 9.46 TYROBP SYK HCST APOE
2 signaling receptor activity GO:0038023 9.26 TREML4 TREML2 TREM2 TREM1
3 lipoprotein particle binding GO:0071813 8.62 TREM2 APOE

Sources for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
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48 NCI
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50 NDF-RT
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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