KEGG DISEASE: Paget disease of bone

DISEASE: Paget disease of bone

Entry

H00437                      Disease

Name

Paget disease of bone

Description

Paget disease of bone (PDB) are rare inherited osteolytic disorders that show phenotypic overlap. Patients with these diseases carry mutations in RANK/TNFRSF11A, OPG/TNFRSF11B or SQSTM1, resulting in activation of RANKL-RANK signaling axis with increases in bone resorption. Hearing impairment and tooth loss is common. Apart from juvenile-onset Paget's disease (PDB5), the condition is inherited as an autosomal dominant trait.

Category

Musculoskeletal disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
15 Diseases of the musculoskeletal system or connective tissue
  Osteopathies or chondropathies
   FB85  Paget disease of bone
    H00437  Paget disease of bone
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06516  TNF signaling
   H00437  Paget disease of bone
Cellular process
  nt06532  Autophagy
   H00437  Paget disease of bone
  nt06536  Mitophagy
   H00437  Paget disease of bone

Pathway

hsa04140

Autophagy - animal

hsa04137

Mitophagy - animal

hsa04380

Osteoclast differentiation

hsa04060

Cytokine-cytokine receptor interaction

hsa04064

NF-kappa B signaling pathway

Network

nt06516 TNF signaling
nt06532 Autophagy
nt06536 Mitophagy

Gene

(PDB2) TNFRSF11A [HSA:8792] [KO:K05147]
(PDB3) SQSTM1 [HSA:8878] [KO:K14381]
(PDB5) TNFRSF11B [HSA:4982] [KO:K05148]
(PDB6) ZNF687 [HSA:57592] [KO:K24375]

Drug

Calcitonin salmon [DR:D00249]
Etidronate disodium [DR:D00314]
Pamidronate disodium [DR:D00941]
Alendronate sodium [DR:D00939]
Risedronate sodium [DR:D00942]
Sodium risedronate hydrate [DR:D03234]
Risedronate sodium monohydrate [DR:D11570]
Zoledronic acid [DR:D01968]

Other DBs

ICD-11:

FB85

MeSH:

D010001

OMIM:

602080 167250 239000 616833

Reference

PMID:16831914

Authors

Whyte MP

Title

Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling.

Journal

Ann N Y Acad Sci 1068:143-64 (2006)
DOI:10.1196/annals.1346.016

Reference

PMID:10615125 (TNFRSF11A)

Authors

Hughes AE, Ralston SH, Marken J, Bell C, MacPherson H, Wallace RG, van Hul W, Whyte MP, Nakatsuka K, Hovy L, Anderson DM

Title

Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis.

Journal

Nat Genet 24:45-8 (2000)
DOI:10.1038/71667

Reference

PMID:11992264 (SQSTM1)

Authors

Laurin N, Brown JP, Morissette J, Raymond V

Title

Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone.

Journal

Am J Hum Genet 70:1582-8 (2002)
DOI:10.1086/340731

Reference

PMID:12124406 (TNFRSF11B)

Authors

Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH, Mumm S

Title

Osteoprotegerin deficiency and juvenile Paget's disease.

Journal

N Engl J Med 347:175-84 (2002)
DOI:10.1056/NEJMoa013096

Reference

PMID:26849110 (ZNF687)

Authors

Divisato G, Formicola D, Esposito T, Merlotti D, Pazzaglia L, Del Fattore A, Siris E, Orcel P, Brown JP, Nuti R, Strazzullo P, Benassi MS, Cancela ML, Michou L, Rendina D, Gennari L, Gianfrancesco F

Title

ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor.

Journal

Am J Hum Genet 98:275-86 (2016)
DOI:10.1016/j.ajhg.2015.12.016

LinkDB

» Japanese version

DISEASE: Familial expansile osteolysis

Entry

H02042                      Disease

Name

Familial expansile osteolysis

Description

Familial expansile osteolysis (FEO) is a rare autosomal dominant disorder causing bone dysplasia. It is characterized by increased osteoclast activity, medullary expansion, and hearing and dental problems. The mutations in the TNFRSF11A gene encoding RANK have been identified. FEO is similar in some respects to Paget's disease but distinct enough in its clinical, radiological and histological findings to be classified as a separate disease.