PLOSL2
MCID: PLY181
MIFTS: 27

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2 (PLOSL2)

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 2:

Name: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2 57 72 29 6
Plosl2 57 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
four clinical stages
1 - latent phase with normal development into early childhood
2 - osseous stage with joint pain and fractures in second-third decade
3 - early neurologic stage manifesting as frontal lobe syndrome
4 - late neurologic stage with profound dementia and death by age 50


HPO:

31
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

OMIM® : 57 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years (summary by Klunemann et al., 2005). For a discussion of genetic heterogeneity of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, see 221770. (618193) (Updated 20-May-2021)

MalaCards based summary : Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2, is also known as plosl2. An important gene associated with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2 is TREM2 (Triggering Receptor Expressed On Myeloid Cells 2). Affiliated tissues include bone and thalamus, and related phenotypes are cerebral cortical atrophy and hypoplasia of the corpus callosum

UniProtKB/Swiss-Prot : 72 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2: An autosomal recessive disease characterized by presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years.

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

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

Human phenotypes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2:

31 (show all 23)
# Description HPO Frequency HPO Source Accession
1 cerebral cortical atrophy 31 very rare (1%) HP:0002120
2 hypoplasia of the corpus callosum 31 very rare (1%) HP:0002079
3 leukoencephalopathy 31 very rare (1%) HP:0002352
4 caudate atrophy 31 very rare (1%) HP:0002340
5 basal ganglia calcification 31 very rare (1%) HP:0002135
6 t2 hypointense thalamus 31 very rare (1%) HP:0012690
7 eeg abnormality 31 HP:0002353
8 gait disturbance 31 HP:0001288
9 osteopenia 31 HP:0000938
10 myoclonus 31 HP:0001336
11 arthralgia 31 HP:0002829
12 memory impairment 31 HP:0002354
13 bone cyst 31 HP:0012062
14 babinski sign 31 HP:0003487
15 aphasia 31 HP:0002381
16 dementia 31 HP:0000726
17 disinhibition 31 HP:0000734
18 agnosia 31 HP:0010524
19 pathologic fracture 31 HP:0002756
20 apraxia 31 HP:0002186
21 primitive reflex 31 HP:0002476
22 cns demyelination 31 HP:0007305
23 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
gait disturbance
myoclonus
leukoencephalopathy
aphasia
more
Neurologic Behavioral Psychiatric Manifestations:
disinhibition
euphoria
frontal lobe syndrome (onset third decade)
loss of judgment

Skeletal Hands:
carpal radiolucent cysts
metacarpal radiolucent cysts
phalangeal radiolucent cysts

Skeletal:
osteopenia

Skeletal Limbs:
joint pain (onset third decade)
pathologic fractures (onset third decade)
long bone metaphyseal radiolucent cysts

Skeletal Feet:
tarsal radiolucent cysts

Clinical features from OMIM®:

618193 (Updated 20-May-2021)

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

Search Clinical Trials , NIH Clinical Center for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2

Genetic Tests for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Genetic tests related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2:

# Genetic test Affiliating Genes
1 Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2 29 TREM2

Anatomical Context for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

MalaCards organs/tissues related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2:

40
Bone, Thalamus

Publications for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Articles related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2:

(show all 11)
# Title Authors PMID Year
1
The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. 57 6
15883308 2005
2
Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. 6 57
12080485 2002
3
Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile dementia. 57 6
6681564 1983
4
Evidence of CNS β-amyloid deposition in Nasu-Hakola disease due to the TREM2 Q33X mutation. 6
29142083 2017
5
Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment. 6
28768830 2017
6
Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms. 6
27995897 2016
7
Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus. 6
25615530 2015
8
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): a new report of an Italian woman and review of the literature. 6
23399524 2013
9
DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. 6
12925681 2003
10
An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene. 6
12754369 2003
11
CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. 57
11402114 2001

Variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

ClinVar genetic disease variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2:

6 (show all 28)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TREM2 TREM2, IVS3DS, T-C, +2 SNV Pathogenic 5216 GRCh37:
GRCh38:
2 TREM2 NM_018965.3(TREM2):c.40G>T (p.Glu14Ter) SNV Pathogenic 56724 rs386834143 GRCh37: 6:41130781-41130781
GRCh38: 6:41163043-41163043
3 TREM2 NM_018965.3(TREM2):c.97C>T (p.Gln33Ter) SNV Pathogenic 5219 rs104894002 GRCh37: 6:41129295-41129295
GRCh38: 6:41161557-41161557
4 TREM2 NM_018965.3(TREM2):c.233G>A (p.Trp78Ter) SNV Likely pathogenic 5213 rs104893998 GRCh37: 6:41129159-41129159
GRCh38: 6:41161421-41161421
5 TREM2 NM_018965.3(TREM2):c.377T>G (p.Val126Gly) SNV Likely pathogenic 5218 rs121908402 GRCh37: 6:41129015-41129015
GRCh38: 6:41161277-41161277
6 TREM2 NM_018965.3(TREM2):c.132G>A (p.Trp44Ter) SNV Likely pathogenic 5217 rs104894001 GRCh37: 6:41129260-41129260
GRCh38: 6:41161522-41161522
7 TREM2 NM_018965.3(TREM2):c.558G>T (p.Lys186Asn) SNV Uncertain significance 5214 rs28937876 GRCh37: 6:41126729-41126729
GRCh38: 6:41158991-41158991
8 TREM2 NM_018965.3(TREM2):c.401A>G (p.Asp134Gly) SNV Uncertain significance 5215 rs28939079 GRCh37: 6:41127611-41127611
GRCh38: 6:41159873-41159873
9 TREM2 NM_018965.3(TREM2):c.-51G>A SNV Uncertain significance 356682 rs3747741 GRCh37: 6:41130871-41130871
GRCh38: 6:41163133-41163133
10 TREM2 NM_018965.3(TREM2):c.254C>T (p.Thr85Ile) SNV Uncertain significance 356679 rs368255898 GRCh37: 6:41129138-41129138
GRCh38: 6:41161400-41161400
11 TREM2 NM_018965.3(TREM2):c.115G>A (p.Asp39Asn) SNV Uncertain significance 356680 rs764816591 GRCh37: 6:41129277-41129277
GRCh38: 6:41161539-41161539
12 TREM2 NM_018965.3(TREM2):c.393C>T (p.Asp131=) SNV Uncertain significance 356677 rs139607688 GRCh37: 6:41127619-41127619
GRCh38: 6:41159881-41159881
13 TREM2 NM_018965.3(TREM2):c.690G>A (p.Thr230=) SNV Uncertain significance 356675 rs199795809 GRCh37: 6:41126505-41126505
GRCh38: 6:41158767-41158767
14 TREM2 NM_018965.4(TREM2):c.574G>A (p.Ala192Thr) SNV Uncertain significance 904021 GRCh37: 6:41126713-41126713
GRCh38: 6:41158975-41158975
15 TREM2 NM_018965.4(TREM2):c.482+7C>T SNV Uncertain significance 904022 GRCh37: 6:41127523-41127523
GRCh38: 6:41159785-41159785
16 TREM2 NM_018965.3(TREM2):c.259G>A (p.Asp87Asn) SNV Uncertain significance 261064 rs142232675 GRCh37: 6:41129133-41129133
GRCh38: 6:41161395-41161395
17 TREM2 NM_018965.4(TREM2):c.117C>G (p.Asp39Glu) SNV Uncertain significance 905893 GRCh37: 6:41129275-41129275
GRCh38: 6:41161537-41161537
18 TREM2 NM_018965.4(TREM2):c.*157G>A SNV Uncertain significance 906351 GRCh37: 6:41126345-41126345
GRCh38: 6:41158607-41158607
19 TREM2 NC_000006.12:g.41163180G>A SNV Uncertain significance 906413 GRCh37: 6:41130918-41130918
GRCh38: 6:41163180-41163180
20 TREM2 NM_018965.4(TREM2):c.*156G>T SNV Uncertain significance 907354 GRCh37: 6:41126346-41126346
GRCh38: 6:41158608-41158608
21 TREM2 NM_018965.4(TREM2):c.*148C>T SNV Uncertain significance 907355 GRCh37: 6:41126354-41126354
GRCh38: 6:41158616-41158616
22 TREM2 NM_018965.3(TREM2):c.40+13C>T SNV Uncertain significance 356681 rs145658858 GRCh37: 6:41130768-41130768
GRCh38: 6:41163030-41163030
23 TREM2 NM_018965.3(TREM2):c.399G>T (p.Leu133=) SNV Uncertain significance 290058 rs144250872 GRCh37: 6:41127613-41127613
GRCh38: 6:41159875-41159875
24 TREM2 NM_018965.3(TREM2):c.469C>T (p.His157Tyr) SNV Likely benign 196494 rs2234255 GRCh37: 6:41127543-41127543
GRCh38: 6:41159805-41159805
25 TREM2 NM_018965.4(TREM2):c.*48A>T SNV Likely benign 907356 GRCh37: 6:41126454-41126454
GRCh38: 6:41158716-41158716
26 TREM2 NM_018965.3(TREM2):c.*73G>A SNV Likely benign 235387 rs2234258 GRCh37: 6:41126429-41126429
GRCh38: 6:41158691-41158691
27 TREM2 NM_018965.4(TREM2):c.668C>T (p.Thr223Ile) SNV Benign 714394 rs138355759 GRCh37: 6:41126619-41126619
GRCh38: 6:41158881-41158881
28 TREM2 NM_018965.3(TREM2):c.*30G>A SNV Benign 356674 rs75272959 GRCh37: 6:41126472-41126472
GRCh38: 6:41158734-41158734

UniProtKB/Swiss-Prot genetic disease variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2:

72
# Symbol AA change Variation ID SNP ID
1 TREM2 p.Val126Gly VAR_081680 rs121908402

Expression for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Search GEO for disease gene expression data for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2.

Pathways for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

GO Terms for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

Sources for Polycystic Lipomembranous Osteodysplasia with Sclerosing...

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