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 57 72 29 6
Nasu-Hakola Disease 57 12 25 20 43 58 72 36 29 13 54 15
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 12 25 20 43 58 29 44 39 70
Plosl 57 12 25 20 43 58
Nhd 57 12 20 43 58 72
Presenile Dementia with Bone Cysts 57 12 20 43 72
Plo-Sl 12 43 58
Dementia, Progressive, with Lipomembranous Polycystic Osteodysplasia 57 20
Dementia, Prefrontal, with Bone Cysts 57 20
Brain-Bone-Fat Disease 57 20
Plosl1 57 72
Progressive Dementia with Lipomembranous Polycystic Osteodysplasia; Brain-Bone-Fat Disease 12
Nasu-Hakola Disease; Nhd 57

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®:

57 (Updated 20-May-2021)
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...

GARD : 20 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.

MalaCards based summary : Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1, also known as nasu-hakola disease, is related to solitary bone cyst and basal ganglia calcification, 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 developmental regression and skeletal dysplasia

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.

MedlinePlus Genetics : 43 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® : 57 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) (Updated 20-May-2021)

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 : 72 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 : 73 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 62)
# Related Disease Score Top Affiliating Genes
1 solitary bone cyst 30.9 TYROBP TREM2
2 basal ganglia calcification 30.7 TYROBP TREM2 PSEN1
3 frontotemporal dementia 30.6 TREM2 PSEN1 CSF1R APOE
4 dementia 30.4 TYROBP TREM2 PSEN1 CSF1R APOE
5 osteoarthritis with mild chondrodysplasia 11.2
6 autosomal recessive disease 10.8
7 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 10.7
8 alzheimer disease 10.4
9 hydrocephalus 10.4
10 brain edema 10.4
11 large granular lymphocyte leukemia 10.4 TYROBP HCST
12 amyotrophic lateral sclerosis 1 10.3
13 leukodystrophy 10.3
14 lateral sclerosis 10.3
15 cerebral atrophy 10.3
16 gerstmann syndrome 10.3 PSEN1 APOE
17 simultanagnosia 10.3 PSEN1 APOE
18 visual agnosia 10.3 PSEN1 APOE
19 anosognosia 10.3 PSEN1 APOE
20 progressive non-fluent aphasia 10.3 TREM2 PSEN1
21 semantic dementia 10.3 TREM2 PSEN1 APOE
22 nominal aphasia 10.2 PSEN1 APOE
23 tenosynovial giant cell tumor 10.2 IL34 CSF1R
24 alzheimer disease 17 10.2 APOE AIF1
25 early-onset, autosomal dominant alzheimer disease 10.2 TREM2 PSEN1 CSF1R APOE
26 supranuclear palsy, progressive, 1 10.2 TREM2 PSEN1 APOE
27 toxic encephalopathy 10.2 PSEN1 APOE AIF1
28 creutzfeldt-jakob disease 10.2
29 basal ganglia calcification, idiopathic, 1 10.2
30 metachromatic leukodystrophy 10.2
31 myoclonic epilepsy of unverricht and lundborg 10.2
32 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.2
33 bone disease 10.2
34 bone resorption disease 10.2
35 hypoparathyroidism 10.2
36 status epilepticus 10.2
37 neuroaxonal dystrophy 10.2
38 acute kidney failure 10.2
39 early myoclonic encephalopathy 10.2
40 lysosomal storage disease 10.2
41 peripheral nervous system disease 10.2
42 paraplegia 10.2
43 prion disease 10.2
44 neuropathy 10.2
45 myotonic dystrophy 10.2
46 persistent vegetative state 10.2
47 tremor 10.2
48 dementia, lewy body 10.1 TREM2 PSEN1 APOE AIF1
49 alzheimer disease 2 10.1 PSEN1 APOE
50 pick disease of brain 10.1 TREM2 PSEN1 APOE AIF1

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 developmental regression 58 31 hallmark (90%) Very frequent (99-80%) HP:0002376
2 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
3 reduced bone mineral density 58 31 hallmark (90%) Very frequent (99-80%) HP:0004349
4 irritability 58 31 hallmark (90%) Very frequent (99-80%) HP:0000737
5 arthralgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002829
6 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
7 ventriculomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002119
8 abnormality of epiphysis morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0005930
9 memory impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0002354
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 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
18 neurological speech impairment 58 31 frequent (33%) Frequent (79-30%) HP:0002167
19 cerebral calcification 58 31 frequent (33%) Frequent (79-30%) HP:0002514
20 chorea 58 31 frequent (33%) Frequent (79-30%) HP:0002072
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 seizures 58 Frequent (79-30%)
28 eeg abnormality 31 HP:0002353
29 gait disturbance 31 HP:0001288
30 behavioral abnormality 58 Very frequent (99-80%)
31 myoclonus 31 HP:0001336
32 abnormality of movement 58 Frequent (79-30%)
33 babinski sign 31 HP:0003487
34 hypoplasia of the corpus callosum 31 HP:0002079
35 leukoencephalopathy 31 HP:0002352
36 cerebral atrophy 31 HP:0002059
37 aggressive behavior 31 HP:0000718
38 abnormality of the hand 31 HP:0001155
39 urinary incontinence 31 HP:0000020
40 pathologic fracture 31 HP:0002756
41 apraxia 31 HP:0002186
42 caudate atrophy 31 HP:0002340
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 basal ganglia calcification 31 HP:0002135

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
spasticity
gait disturbance
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 (Updated 20-May-2021)

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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.1 AIF1 APOE CSF1R CX3CR1 HCST IL34
2 immune system MP:0005387 10.03 AIF1 APOE CLEC5A CSF1R CX3CR1 HCST
3 no phenotypic analysis MP:0003012 9.5 APOE CSF1R CX3CR1 HCST IL34 SYK
4 skeleton MP:0005390 9.36 AIF1 APOE CLEC5A CSF1R HCST PLXNA1

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, Monocytes, Bone Marrow, Thalamus, Kidney

Publications for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Articles related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:

(show top 50) (show all 160)
# Title Authors PMID Year
1
The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. 61 54 25 57 6
15883308 2005
2
Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. 25 57 6 61 54
10888890 2000
3
Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. 61 57 25 6
12370476 2002
4
DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. 25 6 54 61
12925681 2003
5
Mutations in TREM2 lead to pure early-onset dementia without bone cysts. 61 6 25
18546367 2008
6
CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. 25 57 61
11402114 2001
7
[Polycystic lipomembranous osteodysplasia]. 25 6
11109371 2000
8
Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13. 57 25
9463329 1998
9
Vascular changes and blood-brain barrier damage in the pathogenesis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy). 57 25
8085433 1994
10
A novel compound heterozygous mutation in the DAP12 gene in a patient with Nasu-Hakola disease. 61 25 54
17125796 2007
11
Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium. 57 54
9828133 1998
12
Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases. 61 25
30127720 2018
13
A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature. 61 25
28214109 2017
14
Targeted sequencing approach to identify genetic mutations in Nasu-Hakola disease. 25 61
27904822 2016
15
A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate. 61 25
26598595 2015
16
Membranous lipodystrophy: skeletal findings on CT and MRI. 61 25
24777445 2014
17
Homozygous TREM2 mutation in a family with atypical frontotemporal dementia. 25 61
24910390 2014
18
C9ORF72 expansion does not affect the phenotype in Nasu-Hakola disease with the DAP12 mutation. 61 25
24612676 2014
19
Extremity manifestations and surgical treatment for nasu hakola disease. 25 61
24711942 2014
20
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): a new report of an Italian woman and review of the literature. 61 25
23399524 2013
21
Gray matter lesions in Nasu-Hakola disease: a report on three autopsy cases. 25 61
20880319 2011
22
Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease. 25 61
18404378 2009
23
Regional cerebral blood flow in a patient with Nasu-Hakola disease. 25 61
16097640 2005
24
Impaired differentiation of osteoclasts in TREM-2-deficient individuals. 61 25
12913093 2003
25
Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. 25 61
12080485 2002
26
Hypothalamic haemorrhage and thalamus degeneration in a case of Nasu-Hakola disease with hallucinatory symptoms and central hypothermia. 25 61
10787346 2000
27
Nasu-Hakola syndrome: polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy and presenile dementia. 57
9321763 1997
28
Nasu-Hakola disease (membranous lipodystrophy). Clinical, histopathological and biochemical studies of three cases. 25 61
2746291 1989
29
Hereditary polycystic osteodysplasia with progressive dementia in Sweden. 57
77975 1978
30
Membranous lipodystrophy of bone. 57
579591 1978
31
Lipomembranous polycystic osteodysplasia. 57
827851 1976
32
Bone mineral content in hereditary polycystic osteodysplasia associated with progressive dementia. 57
1189965 1975
33
A new hereditary disease with progressive dementia and polycystic osteodysplasia: neuroradiological analysis of seven cases. 57
4764488 1973
34
Behavioral Variant Frontotemporal Dementia-like Syndrome With Novel Heterozygous TREM2 Frameshift Mutation. 25
30106757 2019
35
The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders. 25
30033062 2018
36
Parental influence on human germline de novo mutations in 1,548 trios from Iceland. 25
28959963 2017
37
TREM2 in CNS homeostasis and neurodegenerative disease. 25
26337043 2015
38
Word list learning in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. 25
23569454 2013
39
Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. 25
23318515 2013
40
Rorschach assessment of personality functioning in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. 25
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. 25
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. 61 54
17407101 2007
46
TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. 61 54
16418779 2006
47
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
48
Radiologic bone changes of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. 25
7079784 1982
49
A lipid metabolic disease-"membranous lipodystrophy"-an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. 25
4800725 1973
50
Neuropathological Alzheimer's Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes. 61
33216037 2021

Variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

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

6 (show all 43)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TYROBP NG_009304.1:g.2160_7401del Deletion Pathogenic 192243 GRCh37: 19:36396786-36402027
GRCh38: 19:35905884-35911125
2 TREM2 NM_018965.3(TREM2):c.233G>A (p.Trp78Ter) SNV Pathogenic 5213 rs104893998 GRCh37: 6:41129159-41129159
GRCh38: 6:41161421-41161421
3 TREM2 NM_018965.3(TREM2):c.377T>G (p.Val126Gly) SNV Pathogenic 5218 rs121908402 GRCh37: 6:41129015-41129015
GRCh38: 6:41161277-41161277
4 TREM2 NM_018965.3(TREM2):c.97C>T (p.Gln33Ter) SNV Pathogenic 5219 rs104894002 GRCh37: 6:41129295-41129295
GRCh38: 6:41161557-41161557
5 TYROBP NM_003332.4(TYROBP):c.2T>C (p.Met1Thr) SNV Pathogenic 5797 rs104894732 GRCh37: 19:36399129-36399129
GRCh38: 19:35908227-35908227
6 TREM2 NM_018965.3(TREM2):c.113A>G (p.Tyr38Cys) SNV Pathogenic 192241 rs797044603 GRCh37: 6:41129279-41129279
GRCh38: 6:41161541-41161541
7 TREM2 NM_018965.3(TREM2):c.197C>T (p.Thr66Met) SNV Pathogenic 192242 rs201258663 GRCh37: 6:41129195-41129195
GRCh38: 6:41161457-41161457
8 TYROBP TYROBP, 1-BP DEL, 141G Deletion Pathogenic 5796 GRCh37:
GRCh38:
9 TYROBP TYROBP, EX1-4DEL Deletion Pathogenic 5795 GRCh37:
GRCh38:
10 TYROBP NM_003332.4(TYROBP):c.141del (p.Met48fs) Deletion Pathogenic/Likely pathogenic 56395 rs386833840 GRCh37: 19:36398436-36398436
GRCh38: 19:35907534-35907534
11 TREM2 NM_018965.4(TREM2):c.40+4_40+6del Deletion Pathogenic/Likely pathogenic 56723 rs386834142 GRCh37: 6:41130775-41130777
GRCh38: 6:41163037-41163039
12 TREM2 NM_018965.3(TREM2):c.40G>T (p.Glu14Ter) SNV Likely pathogenic 56724 rs386834143 GRCh37: 6:41130781-41130781
GRCh38: 6:41163043-41163043
13 TREM2 NM_018965.3(TREM2):c.482+2T>C SNV Likely pathogenic 56725 rs386834144 GRCh37: 6:41127528-41127528
GRCh38: 6:41159790-41159790
14 TYROBP NM_003332.4(TYROBP):c.116G>A (p.Ser39Asn) SNV Likely pathogenic 56394 rs386833839 GRCh37: 19:36398461-36398461
GRCh38: 19:35907559-35907559
15 TYROBP NM_003332.4(TYROBP):c.145G>C (p.Gly49Arg) SNV Likely pathogenic 56396 rs386833841 GRCh37: 19:36398432-36398432
GRCh38: 19:35907530-35907530
16 TYROBP NM_003332.4(TYROBP):c.262G>T (p.Glu88Ter) SNV Likely pathogenic 56397 rs386833842 GRCh37: 19:36398134-36398134
GRCh38: 19:35907232-35907232
17 TREM2 NM_018965.3(TREM2):c.269del (p.Gly90fs) Deletion Likely pathogenic 56721 rs386834140 GRCh37: 6:41129123-41129123
GRCh38: 6:41161385-41161385
18 TREM2 NM_018965.3(TREM2):c.313del (p.Ala105fs) Deletion Likely pathogenic 56722 rs386834141 GRCh37: 6:41129079-41129079
GRCh38: 6:41161341-41161341
19 TYROBP NM_003332.4(TYROBP):c.*85C>T SNV Uncertain significance 328890 rs374144427 GRCh37: 19:36395386-36395386
GRCh38: 19:35904484-35904484
20 TYROBP NM_003332.4(TYROBP):c.*5G>A SNV Uncertain significance 328893 rs372703196 GRCh37: 19:36395466-36395466
GRCh38: 19:35904564-35904564
21 TYROBP NM_003332.4(TYROBP):c.-50G>A SNV Uncertain significance 328898 rs371441146 GRCh37: 19:36399180-36399180
GRCh38: 19:35908278-35908278
22 TYROBP NM_003332.4(TYROBP):c.*103T>A SNV Uncertain significance 328889 rs777094340 GRCh37: 19:36395368-36395368
GRCh38: 19:35904466-35904466
23 TREM2 NM_018965.3(TREM2):c.*111A>G SNV Uncertain significance 356673 rs753777378 GRCh37: 6:41126391-41126391
GRCh38: 6:41158653-41158653
24 TYROBP NM_003332.4(TYROBP):c.-34C>T SNV Uncertain significance 328897 rs199931680 GRCh37: 19:36399164-36399164
GRCh38: 19:35908262-35908262
25 TYROBP NM_003332.4(TYROBP):c.46C>T (p.Leu16=) SNV Uncertain significance 732760 rs147393700 GRCh37: 19:36399085-36399085
GRCh38: 19:35908183-35908183
26 TYROBP NM_003332.4(TYROBP):c.*154T>C SNV Uncertain significance 890876 GRCh37: 19:36395317-36395317
GRCh38: 19:35904415-35904415
27 TYROBP NM_003332.4(TYROBP):c.230-3C>T SNV Uncertain significance 892112 GRCh37: 19:36398169-36398169
GRCh38: 19:35907267-35907267
28 TYROBP NM_003332.4(TYROBP):c.180C>G (p.Ala60=) SNV Uncertain significance 892113 GRCh37: 19:36398397-36398397
GRCh38: 19:35907495-35907495
29 TYROBP NM_003332.4(TYROBP):c.140T>C (p.Val47Ala) SNV Uncertain significance 892114 GRCh37: 19:36398437-36398437
GRCh38: 19:35907535-35907535
30 TYROBP NM_003332.4(TYROBP):c.112G>A (p.Val38Met) SNV Uncertain significance 892115 GRCh37: 19:36398465-36398465
GRCh38: 19:35907563-35907563
31 TYROBP NM_003332.4(TYROBP):c.111G>A (p.Thr37=) SNV Uncertain significance 737347 rs200694727 GRCh37: 19:36398466-36398466
GRCh38: 19:35907564-35907564
32 TREM2 NM_018965.3(TREM2):c.514C>T (p.Pro172Ser) SNV Likely benign 522336 rs781302866 GRCh37: 6:41126773-41126773
GRCh38: 6:41159035-41159035
33 TREM2 NM_018965.3(TREM2):c.399G>T (p.Leu133=) SNV Likely benign 290058 rs144250872 GRCh37: 6:41127613-41127613
GRCh38: 6:41159875-41159875
34 TREM2 NM_018965.3(TREM2):c.632T>C (p.Leu211Pro) SNV Likely benign 356676 rs2234256 GRCh37: 6:41126655-41126655
GRCh38: 6:41158917-41158917
35 TREM2 NM_018965.3(TREM2):c.287C>A (p.Thr96Lys) SNV Likely benign 356678 rs2234253 GRCh37: 6:41129105-41129105
GRCh38: 6:41161367-41161367
36 TYROBP NM_003332.3(TYROBP):c.94+10G>C SNV Benign 328895 rs55746266 GRCh37: 19:36398622-36398622
GRCh38: 19:35907720-35907720
37 TYROBP NM_003332.4(TYROBP):c.*25A>C SNV Benign 328892 rs1802029 GRCh37: 19:36395446-36395446
GRCh38: 19:35904544-35904544
38 TYROBP NM_003332.4(TYROBP):c.123C>G (p.Gly41=) SNV Benign 328894 rs111477177 GRCh37: 19:36398454-36398454
GRCh38: 19:35907552-35907552
39 TYROBP NM_003332.4(TYROBP):c.*140T>C SNV Benign 328888 rs113207157 GRCh37: 19:36395331-36395331
GRCh38: 19:35904429-35904429
40 TYROBP NM_003332.4(TYROBP):c.*83C>T SNV Benign 328891 rs14715 GRCh37: 19:36395388-36395388
GRCh38: 19:35904486-35904486
41 TYROBP NM_003332.3(TYROBP):c.68G>A (p.Arg23His) SNV Benign 328896 rs79272253 GRCh37: 19:36398658-36398658
GRCh38: 19:35907756-35907756
42 TYROBP NM_003332.4(TYROBP):c.163G>T (p.Val55Leu) SNV Benign 196360 rs77782321 GRCh37: 19:36398414-36398414
GRCh38: 19:35907512-35907512
43 TREM2 NM_018965.3(TREM2):c.185G>A (p.Arg62His) SNV Benign 445645 rs143332484 GRCh37: 6:41129207-41129207
GRCh38: 6:41161469-41161469

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
13.36 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
2
Show member pathways
12.94 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
3
Show member pathways
12.23 TYROBP TREM2 SYK SIRPB1 CSF1R
4 12.16 TREM2 PSEN1 PLXNA1 APOE
5 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 membrane GO:0016020 10.16 TYROBP TREML2 TREML1 TREM2 TREM1 TMEM119
2 integral component of membrane GO:0016021 10.13 TYROBP TREML2 TREML1 TREM2 TREM1 TMEM119
3 plasma membrane GO:0005886 9.89 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
4 integral component of plasma membrane GO:0005887 9.76 TYROBP TREM2 SIRPB1 PSEN1 PLXNA1 CX3CR1
5 cell surface GO:0009986 9.32 TYROBP TREML4 TREML2 TREML1 SIRPB1 PSEN1

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

(show all 32)
# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 10.05 TYROBP TREML4 SYK IL34 CSF1R CLEC5A
2 negative regulation of apoptotic process GO:0043066 10.01 TREM2 PSEN1 CSF1R CLEC5A AIF1
3 positive regulation of gene expression GO:0010628 9.99 TYROBP TREM2 TMEM119 PSEN1 IL34
4 regulation of gene expression GO:0010468 9.95 TREM2 PSEN1 APOE AIF1
5 positive regulation of interleukin-6 production GO:0032755 9.78 TYROBP SYK AIF1
6 positive regulation of tumor necrosis factor production GO:0032760 9.77 TYROBP SYK PSEN1
7 response to ischemia GO:0002931 9.69 TREM2 CX3CR1 CSF1R
8 positive regulation of dendritic spine development GO:0060999 9.65 PSEN1 APOE
9 apoptotic cell clearance GO:0043277 9.65 TYROBP TREM2
10 cellular defense response GO:0006968 9.65 TYROBP CX3CR1 CLEC5A
11 regulation of innate immune response GO:0045088 9.64 TREM2 APOE
12 positive regulation of superoxide anion generation GO:0032930 9.64 TYROBP SYK
13 positive regulation of chemotaxis GO:0050921 9.63 TREM2 AIF1
14 positive regulation of macrophage chemotaxis GO:0010759 9.63 IL34 CSF1R
15 positive regulation of protein phosphorylation GO:0001934 9.63 TREM2 TMEM119 PSEN1 IL34 CSF1R AIF1
16 positive regulation of calcium-mediated signaling GO:0050850 9.62 TREM2 SYK
17 astrocyte activation GO:0048143 9.62 TREM2 PSEN1
18 amyloid precursor protein metabolic process GO:0042982 9.58 PSEN1 APOE
19 regulation of resting membrane potential GO:0060075 9.57 TREM2 PSEN1
20 positive regulation by host of viral process GO:0044794 9.56 CSF1R APOE
21 positive regulation of microglial cell migration GO:1904141 9.55 TREM2 CX3CR1
22 positive regulation of amyloid-beta clearance GO:1900223 9.54 TREM2 APOE
23 osteoclast differentiation GO:0030316 9.54 TYROBP TREM2 CSF1R
24 positive regulation of macrophage proliferation GO:0120041 9.52 IL34 CSF1R
25 negative regulation of long-term synaptic potentiation GO:1900272 9.5 TYROBP CX3CR1 APOE
26 regulation of immune response GO:0050776 9.5 TYROBP TREML4 TREML2 TREML1 TREM2 TREM1
27 neutrophil activation involved in immune response GO:0002283 9.49 TYROBP SYK
28 positive regulation of macrophage fusion GO:0034241 9.46 TYROBP TREM2
29 positive regulation of amyloid fibril formation GO:1905908 9.43 PSEN1 APOE
30 microglial cell proliferation GO:0061518 9.43 TREM2 IL34 CSF1R
31 microglial cell activation involved in immune response GO:0002282 9.4 TYROBP TREM2
32 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 activity GO:0038023 9.02 TREML4 TREML2 TREM2 TREM1 PLXNA1
2 lipoprotein particle binding GO:0071813 8.96 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
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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