MCID: MLT138
MIFTS: 40

Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

MalaCards integrated aliases for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum:

Name: Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum 58
Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum Disorders 6
Nodulosis-Arthropathy-Osteolysis Syndrome 58
Torg-Winchester Syndrome 58
Mona Spectrum 58
Nao Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
multicentric osteolysis-nodulosis-arthropathy spectrum
Inheritance: Autosomal recessive; Age of onset: Childhood,Infancy; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

MalaCards based summary : Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum, also known as multicentric osteolysis-nodulosis-arthropathy spectrum disorders, is related to multicentric osteolysis, nodulosis, and arthropathy and winchester syndrome. An important gene associated with Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum is MMP2 (Matrix Metallopeptidase 2), and among its related pathways/superpathways are Development Endothelin-1/EDNRA signaling and Colorectal Cancer Metastasis. The drugs Pamidronate and Zoledronic Acid have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and ovary, and related phenotypes are osteopenia and arthritis

Related Diseases for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Graphical network of the top 20 diseases related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum:



Diseases related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Symptoms & Phenotypes for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Human phenotypes related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum:

58 31 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteopenia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000938
2 arthritis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001369
3 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%) HP:0001999
4 osteoporosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000939
5 abnormal hand morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0005922
6 hirsutism 58 31 hallmark (90%) Very frequent (99-80%) HP:0001007
7 carpal osteolysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001495
8 arthropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003040
9 osteolysis involving tarsal bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0006234
10 subcutaneous nodule 58 31 frequent (33%) Frequent (79-30%) HP:0001482
11 brachycephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000248
12 abnormal form of the vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0003312
13 broad clavicles 58 31 frequent (33%) Frequent (79-30%) HP:0000916
14 broad metacarpals 58 31 frequent (33%) Frequent (79-30%) HP:0001230
15 sclerotic cranial sutures 58 31 frequent (33%) Frequent (79-30%) HP:0005441
16 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
17 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
18 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
19 type i diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0100651
20 atrioventricular block 58 31 occasional (7.5%) Occasional (29-5%) HP:0001678
21 atrial septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001631
22 bicuspid aortic valve 58 31 occasional (7.5%) Occasional (29-5%) HP:0001647
23 coarctation of aorta 58 31 occasional (7.5%) Occasional (29-5%) HP:0001680
24 mitral valve prolapse 58 31 occasional (7.5%) Occasional (29-5%) HP:0001634
25 double outlet right ventricle 58 31 occasional (7.5%) Occasional (29-5%) HP:0001719
26 iris coloboma 58 31 occasional (7.5%) Occasional (29-5%) HP:0000612
27 polycystic ovaries 58 31 occasional (7.5%) Occasional (29-5%) HP:0000147
28 increased susceptibility to fractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002659
29 papilledema 58 31 occasional (7.5%) Occasional (29-5%) HP:0001085
30 omphalocele 58 31 occasional (7.5%) Occasional (29-5%) HP:0001539
31 pterygium 58 31 occasional (7.5%) Occasional (29-5%) HP:0001059
32 abnormality of the orbital region 58 31 occasional (7.5%) Occasional (29-5%) HP:0000315
33 nodular goiter 58 31 occasional (7.5%) Occasional (29-5%) HP:0005994
34 premature thelarche 58 31 occasional (7.5%) Occasional (29-5%) HP:0010314
35 abnormality of the cardiovascular system 58 Frequent (79-30%)
36 osteolysis 58 Very frequent (99-80%)
37 localized skin lesion 58 Frequent (79-30%)
38 osteolysis involving bones of the lower limbs 58 Very frequent (99-80%)
39 osteolysis involving bones of the upper limbs 58 Very frequent (99-80%)

Drugs & Therapeutics for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Drugs for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Pamidronate Approved 40391-99-9 4674
2
Zoledronic Acid Approved 118072-93-8 68740
3 Diphosphonates

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Bisphosphonates in Multicentric Osteolysis, Nodulosis and Arthropathy (MONA) Spectrum Disorder - an Alternative Therapeutic Approach Completed NCT02823925 Pamidronate or Zoledronate

Search NIH Clinical Center for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Genetic Tests for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Anatomical Context for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

MalaCards organs/tissues related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum:

40
Bone, Skin, Ovary, Tongue

Publications for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Articles related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum:

(show all 15)
# Title Authors PMID Year
1
Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome. 61 6
17059372 2007
2
Multicentric Osteolysis Nodulosis and Arthropathy 6
27413800 2016
3
Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. 6
22922033 2012
4
A novel homozygous MMP2 mutation in a family with Winchester syndrome. 6
16542393 2006
5
Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. 6
15691365 2005
6
Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. 6
11431697 2001
7
Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. 6
10356396 1999
8
[Biochemical and ultrastructural study of two familial cases of Winchester syndrome]. 6
2625626 1989
9
An interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptides. 6
6525336 1984
10
A new acid mucopolysaccharidosis with skeletal deformities simulating rheumatoid arthritis. 6
4238825 1969
11
Identification of drug-target interaction from interactome network with 'guilt-by-association' principle and topology features. 61
26614126 2016
12
A report of three patients with MMP2 associated hereditary osteolysis. 61
22876575 2012
13
A novel homozygous MMP2 mutation in a patient with Torg-Winchester syndrome. 61
20720557 2010
14
Clinical and radiographic findings in two brothers affected with a novel mutation in matrix metalloproteinase 2 gene. 61
19653001 2010
15
Torg-Winchester syndrome: lack of efficacy of pamidronate therapy. 61
17351352 2007

Variations for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

ClinVar genetic disease variations for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum:

6 (show top 50) (show all 57) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MMP2 NM_004530.6(MMP2):c.302G>A (p.Arg101His)SNV Pathogenic 17108 rs121912953 16:55516969-55516969 16:55483057-55483057
2 MMP2 NM_004530.6(MMP2):c.732C>A (p.Tyr244Ter)SNV Pathogenic 17109 rs121912954 16:55519589-55519589 16:55485677-55485677
3 MMP2 NM_004530.6(MMP2):c.1210G>A (p.Glu404Lys)SNV Pathogenic 17110 rs121912955 16:55525742-55525742 16:55491830-55491830
4 MMP2 MMP2, 3-BP DEL, 1488TGGdeletion Pathogenic 17111
5 MMP2 NM_004530.6(MMP2):c.1357del (p.Gly454fs)deletion Pathogenic 17112 rs1567378779 16:55527089-55527089 16:55493177-55493177
6 LPCAT2 NM_017839.5(LPCAT2):c.172-6188G>ASNV Pathogenic 625853 rs1567390809 16:55553232-55553232 16:55519320-55519320
7 MMP2 NM_004530.6(MMP2):c.1858G>A (p.Val620Ile)SNV Conflicting interpretations of pathogenicity 194059 rs41459945 16:55536779-55536779 16:55502867-55502867
8 MMP2 NM_004530.6(MMP2):c.1233G>A (p.Leu411=)SNV Conflicting interpretations of pathogenicity 319757 rs140172728 16:55525765-55525765 16:55491853-55491853
9 MMP2 NM_004530.6(MMP2):c.51C>T (p.Leu17=)SNV Conflicting interpretations of pathogenicity 319746 rs41503347 16:55513442-55513442 16:55479530-55479530
10 MMP2 NM_004530.6(MMP2):c.658+10G>ASNV Conflicting interpretations of pathogenicity 319748 rs201653184 16:55519349-55519349 16:55485437-55485437
11 MMP2 NM_004530.6(MMP2):c.1572C>T (p.Tyr524=)SNV Conflicting interpretations of pathogenicity 319763 rs374801798 16:55530937-55530937 16:55497025-55497025
12 MMP2 NM_004530.6(MMP2):c.1758C>A (p.Asp586Glu)SNV Uncertain significance 319764 rs746772419 16:55532349-55532349 16:55498437-55498437
13 MMP2 NM_004530.6(MMP2):c.*51G>ASNV Uncertain significance 319770 rs200211639 16:55539405-55539405 16:55505493-55505493
14 MMP2 NM_004530.6(MMP2):c.*132T>ASNV Uncertain significance 319771 rs55926431 16:55539486-55539486 16:55505574-55505574
15 MMP2 NM_004530.6(MMP2):c.*212C>TSNV Uncertain significance 319774 rs147506379 16:55539566-55539566 16:55505654-55505654
16 MMP2 NM_004530.6(MMP2):c.*669C>GSNV Uncertain significance 319782 rs17860024 16:55540023-55540023 16:55506111-55506111
17 MMP2 NM_004530.6(MMP2):c.*853A>GSNV Uncertain significance 319783 rs539550309 16:55540207-55540207 16:55506295-55506295
18 MMP2 NM_004530.6(MMP2):c.*872C>TSNV Uncertain significance 319784 rs140455191 16:55540226-55540226 16:55506314-55506314
19 MMP2 NM_004530.6(MMP2):c.-201C>GSNV Uncertain significance 319741 rs886052124 16:55513191-55513191 16:55479279-55479279
20 MMP2 NM_004530.6(MMP2):c.-201_-199CGG[8]short repeat Uncertain significance 319740 rs567092201 16:55513189-55513190 16:55479277-55479278
21 MMP2 NM_004530.6(MMP2):c.1567G>T (p.Val523Leu)SNV Uncertain significance 319762 rs761833659 16:55530932-55530932 16:55497020-55497020
22 MMP2 NM_004530.6(MMP2):c.588C>T (p.Ala196=)SNV Uncertain significance 319747 rs886052125 16:55519269-55519269 16:55485357-55485357
23 MMP2 NM_004530.6(MMP2):c.*170G>ASNV Uncertain significance 319773 rs41280909 16:55539524-55539524 16:55505612-55505612
24 MMP2 NM_004530.6(MMP2):c.*228C>TSNV Uncertain significance 319775 rs886052126 16:55539582-55539582 16:55505670-55505670
25 MMP2 NM_004530.6(MMP2):c.*400G>ASNV Uncertain significance 319777 rs17860021 16:55539754-55539754 16:55505842-55505842
26 MMP2 NM_004530.6(MMP2):c.*551dupduplication Uncertain significance 319780 rs886052128 16:55539895-55539896 16:55505983-55505984
27 MMP2 NM_004530.6(MMP2):c.*1204A>TSNV Uncertain significance 319787 rs758075499 16:55540558-55540558 16:55506646-55506646
28 MMP2 NM_004530.6(MMP2):c.-114G>ASNV Uncertain significance 319742 rs552672554 16:55513278-55513278 16:55479366-55479366
29 MMP2 NM_004530.6(MMP2):c.-7C>ASNV Uncertain significance 319744 rs765195089 16:55513385-55513385 16:55479473-55479473
30 MMP2 NM_004530.6(MMP2):c.-2C>ASNV Uncertain significance 319745 rs777848153 16:55513390-55513390 16:55479478-55479478
31 MMP2 NM_004530.6(MMP2):c.658+13C>TSNV Uncertain significance 319749 rs768031015 16:55519352-55519352 16:55485440-55485440
32 MMP2 NM_004530.6(MMP2):c.1336+11G>ASNV Uncertain significance 319758 rs17859933 16:55525879-55525879 16:55491967-55491967
33 MMP2 NM_004530.6(MMP2):c.*498A>GSNV Uncertain significance 319779 rs886052127 16:55539852-55539852 16:55505940-55505940
34 MMP2 NM_004530.6(MMP2):c.1144G>A (p.Asp382Asn)SNV Uncertain significance 319755 rs555030156 16:55523700-55523700 16:55489788-55489788
35 MMP2 NM_004530.6(MMP2):c.539A>T (p.Asp180Val)SNV Uncertain significance 374345 rs1057518712 16:55519220-55519220 16:55485308-55485308
36 MMP2 NM_004530.6(MMP2):c.1779G>A (p.Glu593=)SNV Uncertain significance 319767 rs202060835 16:55536700-55536700 16:55502788-55502788
37 MMP2 NM_004530.6(MMP2):c.1769+10G>ASNV Uncertain significance 319765 rs201956873 16:55532370-55532370 16:55498458-55498458
38 MMP2 NM_004530.6(MMP2):c.*453C>GSNV Uncertain significance 319778 rs562314074 16:55539807-55539807 16:55505895-55505895
39 MMP2 NM_004530.6(MMP2):c.*627T>CSNV Uncertain significance 319781 rs886052129 16:55539981-55539981 16:55506069-55506069
40 MMP2 NM_004530.6(MMP2):c.*930C>TSNV Uncertain significance 319785 rs886052130 16:55540284-55540284 16:55506372-55506372
41 MMP2 NM_004530.6(MMP2):c.377A>G (p.Tyr126Cys)SNV Uncertain significance 690375 16:55517044-55517044 16:55483132-55483132
42 MMP2 NM_004530.6(MMP2):c.*159T>CSNV Likely benign 319772 rs17860019 16:55539513-55539513 16:55505601-55505601
43 MMP2 NM_004530.6(MMP2):c.*1062C>TSNV Likely benign 319786 rs2052264 16:55540416-55540416 16:55506504-55506504
44 MMP2 NM_004530.6(MMP2):c.1842C>G (p.Pro614=)SNV Likely benign 319769 rs11541998 16:55536763-55536763 16:55502851-55502851
45 MMP2 NM_004530.6(MMP2):c.1098C>T (p.Ala366=)SNV Likely benign 319754 rs16955236 16:55523654-55523654 16:55489742-55489742
46 MMP2 NM_004530.6(MMP2):c.-61G>CSNV Likely benign 319743 rs2287073 16:55513331-55513331 16:55479419-55479419
47 MMP2 NM_004530.6(MMP2):c.750C>T (p.Thr250=)SNV Likely benign 319751 rs1053605 16:55519607-55519607 16:55485695-55485695
48 MMP2 NM_004530.6(MMP2):c.832+12C>TSNV Likely benign 319752 rs17859889 16:55519701-55519701 16:55485789-55485789
49 MMP2 NM_004530.6(MMP2):c.1337-7T>CSNV Benign/Likely benign 319759 rs17859942 16:55527063-55527063 16:55493151-55493151
50 MMP2 NM_004530.6(MMP2):c.1340C>T (p.Ala447Val)SNV Benign/Likely benign 319760 rs17859943 16:55527073-55527073 16:55493161-55493161

Expression for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Search GEO for disease gene expression data for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum.

Pathways for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Pathways related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.96 MMP2 MMP14
2 11.54 MMP2 MMP14
3 11.35 MMP2 MMP14
4
Show member pathways
11.15 MMP2 MMP14
5 10.78 MMP2 MMP14
6 10.41 MMP2 MMP14

GO Terms for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

Cellular components related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 8.62 MMP2 MMP14

Biological processes related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 angiogenesis GO:0001525 9.4 MMP2 MMP14
2 extracellular matrix organization GO:0030198 9.37 MMP2 MMP14
3 response to hypoxia GO:0001666 9.32 MMP2 MMP14
4 extracellular matrix disassembly GO:0022617 9.26 MMP2 MMP14
5 collagen catabolic process GO:0030574 9.16 MMP2 MMP14
6 endodermal cell differentiation GO:0035987 8.96 MMP2 MMP14
7 tissue remodeling GO:0048771 8.62 MMP2 MMP14

Molecular functions related to Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metallopeptidase activity GO:0008237 8.96 MMP2 MMP14
2 metalloendopeptidase activity GO:0004222 8.62 MMP2 MMP14

Sources for Multicentric Osteolysis-Nodulosis-Arthropathy Spectrum

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
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
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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