PDB2
MCID: PGT009
MIFTS: 35

Paget Disease of Bone 2, Early-Onset (PDB2)

Categories: Bone diseases, Cancer diseases, Cardiovascular diseases, Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Paget Disease of Bone 2, Early-Onset

MalaCards integrated aliases for Paget Disease of Bone 2, Early-Onset:

Name: Paget Disease of Bone 2, Early-Onset 57 72 29 6
Pdb2 57 72
Paget Disease of Bone, Type 2, Early-Onset 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
progressive disorder
onset in teens or early twenties


HPO:

31
paget disease of bone 2, early-onset:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course variable expressivity progressive


Classifications:



Summaries for Paget Disease of Bone 2, Early-Onset

UniProtKB/Swiss-Prot : 72 Paget disease of bone 2, early-onset: A form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.

MalaCards based summary : Paget Disease of Bone 2, Early-Onset, also known as pdb2, is related to mammary paget's disease and paget's disease of bone. An important gene associated with Paget Disease of Bone 2, Early-Onset is TNFRSF11A (TNF Receptor Superfamily Member 11a), and among its related pathways/superpathways are RANK Signaling in Osteoclasts and Osteoclast differentiation. Affiliated tissues include bone and brain, and related phenotypes are bilateral conductive hearing impairment and bowing of the long bones

OMIM® : 57 Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. See reviews by Ralston et al. (2008) and Ralston and Albagha (2014). For a discussion of genetic heterogeneity of Paget disease of bone, see 167250. (602080) (Updated 05-Apr-2021)

Related Diseases for Paget Disease of Bone 2, Early-Onset

Diseases in the Paget's Disease of Bone family:

Paget Disease of Bone 3 Paget Disease of Bone 5, Juvenile-Onset
Paget Disease of Bone 2, Early-Onset Paget Disease of Bone 4
Paget Disease of Bone 6

Diseases related to Paget Disease of Bone 2, Early-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 mammary paget's disease 29.3 TNFRSF11A SQSTM1
2 paget's disease of bone 29.1 TNFRSF11A SQSTM1
3 paget disease of bone 3 9.9
4 osteogenic sarcoma 9.9
5 periostitis 9.7 TNFRSF11A SQSTM1
6 familial expansile osteolysis 9.6 TNFRSF11A SQSTM1

Graphical network of the top 20 diseases related to Paget Disease of Bone 2, Early-Onset:



Diseases related to Paget Disease of Bone 2, Early-Onset

Symptoms & Phenotypes for Paget Disease of Bone 2, Early-Onset

Human phenotypes related to Paget Disease of Bone 2, Early-Onset:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 bilateral conductive hearing impairment 31 very rare (1%) HP:0008513
2 bowing of the long bones 31 HP:0006487
3 cranial nerve paralysis 31 HP:0006824
4 abnormality of pelvic girdle bone morphology 31 HP:0002644
5 bone pain 31 HP:0002653
6 osteolysis 31 HP:0002797
7 brain stem compression 31 HP:0002512
8 fractures of the long bones 31 HP:0003084
9 increased susceptibility to fractures 31 HP:0002659
10 tetraparesis 31 HP:0002273
11 vertebral compression fractures 31 HP:0002953
12 premature loss of teeth 31 HP:0006480
13 paraparesis 31 HP:0002385
14 elevated alkaline phosphatase 31 HP:0003155
15 hydroxyprolinuria 31 HP:0003080
16 long-tract signs 31 HP:0002423

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal:
bone pain
mixed regions of osteosclerosis and osteolysis
abnormal uptake of radio-labelled bisphosphates in affected sites on bone scan
deformity or enlargement of bones

Head And Neck Ears:
hearing loss, progressive

Head And Neck Head:
swelling and deformity of the mandible and maxilla

Skeletal Limbs:
deformities and bowing of the long bones

Laboratory Abnormalities:
elevated alkaline phosphatase

Head And Neck Teeth:
premature tooth loss

Skeletal Skull:
swelling and deformity of the mandible and maxilla

Skeletal Hands:
swelling of the proximal and distal interphalangeal joints

Clinical features from OMIM®:

602080 (Updated 05-Apr-2021)

Drugs & Therapeutics for Paget Disease of Bone 2, Early-Onset

Search Clinical Trials , NIH Clinical Center for Paget Disease of Bone 2, Early-Onset

Genetic Tests for Paget Disease of Bone 2, Early-Onset

Genetic tests related to Paget Disease of Bone 2, Early-Onset:

# Genetic test Affiliating Genes
1 Paget Disease of Bone 2, Early-Onset 29 TNFRSF11A

Anatomical Context for Paget Disease of Bone 2, Early-Onset

MalaCards organs/tissues related to Paget Disease of Bone 2, Early-Onset:

40
Bone, Brain

Publications for Paget Disease of Bone 2, Early-Onset

Articles related to Paget Disease of Bone 2, Early-Onset:

(show all 38)
# Title Authors PMID Year
1
Juvenile Paget's disease with heterozygous duplication within TNFRSF11A encoding RANK. 6 57
25063546 2014
2
Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis. 57 6
11771666 2002
3
Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. 6 57
10615125 2000
4
Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration. 6
29959261 2018
5
The evolving genetic risk for sporadic ALS. 6
28642336 2017
6
Absence of the Autophagy Adaptor SQSTM1/p62 Causes Childhood-Onset Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy. 6
27545679 2016
7
Targeted next-generation sequencing assay for detection of mutations in primary myopathies. 6
26627873 2016
8
Evolution of Paget's disease of bone in adults inheriting SQSTM1 mutations. 6
25664955 2015
9
SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles. 6
26208961 2015
10
Genetics of Paget's disease of bone. 57
24988994 2014
11
Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration. 6
24899140 2014
12
Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. 6
23417734 2013
13
Thirteen Chinese patients with sporadic Paget's disease of bone: clinical features, SQSTM1 mutation identification, and functional analysis. 6
22491873 2012
14
Pathogenesis and management of Paget's disease of bone. 57
18620951 2008
15
Paget's disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations. 6
17129171 2007
16
Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget's disease of bone. 6
16691492 2006
17
Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutations. 6
15765181 2005
18
Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences. 6
15176995 2004
19
Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB). 6
15125799 2004
20
Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations. 6
15146436 2004
21
Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. 57
12929927 2003
22
Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease. 6
12374763 2002
23
Paget's disease of bone: evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneity. 57
9626621 1998
24
Genetic linkage of Paget disease of the bone to chromosome 18q. 57
9345096 1997
25
Early-onset Paget's disease of bone in a Mexican family caused by a novel tandem duplication (77dup27) in TNFRSF11A that encodes RANK. 61
31923705 2020
26
Isolation, characterization and growth kinetics of phenol hyper-tolerant bacteria from sewage-fed aquaculture system. 61
31790335 2020
27
Robust DNase activity of the ooplasm can act as a gametic transfection barrier in rainbow trout. 61
31574402 2020
28
Dysosteosclerosis is also caused by TNFRSF11A mutation. 61
29568001 2018
29
Developing a puncture-free in ovo chicken transfection strategy based on bypassing albumen nucleases. 61
28215692 2017
30
Evidence of circulation of the novel border disease virus genotype 8 in chamois. 61
27761745 2017
31
Constructing a Mouse Oct4 Promoter/EGFP Vector, as a Whole-Cellular Reporter to Monitor the Pluripotent State of Cells. 61
23626871 2013
32
Sporadic hyperphosphatasia syndrome featuring periostitis and accelerated skeletal turnover without receptor activator of nuclear factor-kappaB, osteoprotegerin, or sequestosome-1 gene defects. 61
17284635 2007
33
Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling. 61
16831914 2006
34
Heritable disorders of the RANKL/OPG/RANK signaling pathway. 61
15615493 2004
35
Linkage of Paget disease of bone to a novel region on human chromosome 18q23. 61
11742440 2002
36
Paget disease of bone: mapping of two loci at 5q35-qter and 5q31. 61
11473345 2001
37
Familial Paget's disease of bone: nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree. 61
11149487 2001
38
Citrate synthase activity in Escherichia coli harbouring hybrid plasmids containing the gltA gene. 61
6355385 1983

Variations for Paget Disease of Bone 2, Early-Onset

ClinVar genetic disease variations for Paget Disease of Bone 2, Early-Onset:

6 (show top 50) (show all 261)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TNFRSF11A NM_003839.4(TNFRSF11A):c.39_65dup (p.Leu14_Ala22dup) Duplication Pathogenic 6300 rs796051862 GRCh37: 18:59992619-59992620
GRCh38: 18:62325386-62325387
2 TNFRSF11A NM_003839.4(TNFRSF11A):c.49_63dup (p.Leu17_Leu21dup) Duplication Pathogenic 208144 rs1555767678 GRCh37: 18:59992633-59992634
GRCh38: 18:62325400-62325401
3 SQSTM1 NM_003900.5(SQSTM1):c.1165+1G>A SNV Pathogenic 8110 rs796051870 GRCh37: 5:179260783-179260783
GRCh38: 5:179833783-179833783
4 TNFRSF11A NM_003839.4(TNFRSF11A):c.45_62dup (p.Leu16_Leu21dup) Duplication Pathogenic 208143 rs886037749 GRCh37: 18:59992620-59992621
GRCh38: 18:62325387-62325388
5 SQSTM1 NM_003900.5(SQSTM1):c.995C>G (p.Ser332Ter) SNV Pathogenic 642133 rs1185406298 GRCh37: 5:179260612-179260612
GRCh38: 5:179833612-179833612
6 SQSTM1 NM_003900.5(SQSTM1):c.1185dup (p.Glu396Ter) Duplication Pathogenic 835699 GRCh37: 5:179263453-179263454
GRCh38: 5:179836453-179836454
7 SQSTM1 NM_003900.5(SQSTM1):c.1211T>C (p.Met404Thr) SNV Pathogenic 855037 GRCh37: 5:179263481-179263481
GRCh38: 5:179836481-179836481
8 SQSTM1 NM_003900.5(SQSTM1):c.810del (p.Val271fs) Deletion Pathogenic 967349 GRCh37: 5:179260083-179260083
GRCh38: 5:179833083-179833083
9 SQSTM1 NM_003900.5(SQSTM1):c.526_529del (p.Ser176fs) Deletion Pathogenic 503881 rs1331685476 GRCh37: 5:179251079-179251082
GRCh38: 5:179824079-179824082
10 SQSTM1 NM_003900.5(SQSTM1):c.286C>T (p.Arg96Ter) SNV Pathogenic 265782 rs886039782 GRCh37: 5:179250038-179250038
GRCh38: 5:179823038-179823038
11 SQSTM1 NM_003900.5(SQSTM1):c.571G>A (p.Gly191Arg) SNV Uncertain significance 639243 rs781478225 GRCh37: 5:179251221-179251221
GRCh38: 5:179824221-179824221
12 SQSTM1 NM_003900.5(SQSTM1):c.46G>A (p.Ala16Thr) SNV Uncertain significance 423540 rs773552098 GRCh37: 5:179247982-179247982
GRCh38: 5:179820982-179820982
13 TNFRSF11A NM_003839.4(TNFRSF11A):c.*1301G>A SNV Uncertain significance 892547 GRCh37: 18:60053568-60053568
GRCh38: 18:62386335-62386335
14 SQSTM1 NM_003900.5(SQSTM1):c.857C>T (p.Pro286Leu) SNV Uncertain significance 948471 GRCh37: 5:179260134-179260134
GRCh38: 5:179833134-179833134
15 SQSTM1 NM_003900.5(SQSTM1):c.251C>T (p.Thr84Ile) SNV Uncertain significance 951976 GRCh37: 5:179250003-179250003
GRCh38: 5:179823003-179823003
16 SQSTM1 NM_003900.5(SQSTM1):c.85C>T (p.Pro29Ser) SNV Uncertain significance 963309 GRCh37: 5:179248021-179248021
GRCh38: 5:179821021-179821021
17 SQSTM1 NM_003900.5(SQSTM1):c.1160C>T (p.Pro387Leu) SNV Uncertain significance 202211 rs776749939 GRCh37: 5:179260777-179260777
GRCh38: 5:179833777-179833777
18 SQSTM1 NM_003900.5(SQSTM1):c.728G>A (p.Ser243Asn) SNV Uncertain significance 1034452 GRCh37: 5:179252200-179252200
GRCh38: 5:179825200-179825200
19 SQSTM1 NM_003900.5(SQSTM1):c.224T>C (p.Val75Ala) SNV Uncertain significance 1035180 GRCh37: 5:179249976-179249976
GRCh38: 5:179822976-179822976
20 SQSTM1 NM_003900.5(SQSTM1):c.293A>G (p.Tyr98Cys) SNV Uncertain significance 1036874 GRCh37: 5:179250045-179250045
GRCh38: 5:179823045-179823045
21 SQSTM1 NM_003900.5(SQSTM1):c.462C>T (p.Cys154=) SNV Uncertain significance 903991 GRCh37: 5:179251018-179251018
GRCh38: 5:179824018-179824018
22 SQSTM1 NM_003900.5(SQSTM1):c.1037T>C (p.Val346Ala) SNV Uncertain significance 1041858 GRCh37: 5:179260654-179260654
GRCh38: 5:179833654-179833654
23 SQSTM1 NM_003900.5(SQSTM1):c.113C>A (p.Ala38Glu) SNV Uncertain significance 1041910 GRCh37: 5:179248049-179248049
GRCh38: 5:179821049-179821049
24 SQSTM1 NM_003900.5(SQSTM1):c.850T>A (p.Ser284Thr) SNV Uncertain significance 1044688 GRCh37: 5:179260127-179260127
GRCh38: 5:179833127-179833127
25 TNFRSF11A NM_003839.4(TNFRSF11A):c.*2564A>G SNV Uncertain significance 891659 GRCh37: 18:60054831-60054831
GRCh38: 18:62387598-62387598
26 SQSTM1 NM_003900.5(SQSTM1):c.1178G>A (p.Arg393Gln) SNV Uncertain significance 475395 rs200551825 GRCh37: 5:179263448-179263448
GRCh38: 5:179836448-179836448
27 SQSTM1 NM_003900.5(SQSTM1):c.802C>G (p.Leu268Val) SNV Uncertain significance 542158 rs753685955 GRCh37: 5:179260079-179260079
GRCh38: 5:179833079-179833079
28 SQSTM1 NM_003900.5(SQSTM1):c.457G>A (p.Val153Ile) SNV Uncertain significance 571746 rs145056421 GRCh37: 5:179251013-179251013
GRCh38: 5:179824013-179824013
29 SQSTM1 NM_003900.5(SQSTM1):c.711_713GAA[1] (p.Lys238del) Microsatellite Uncertain significance 202213 rs796052214 GRCh37: 5:179252183-179252185
GRCh38: 5:179825183-179825185
30 SQSTM1 NM_003900.5(SQSTM1):c.139C>G (p.Leu47Val) SNV Uncertain significance 664776 rs779786150 GRCh37: 5:179248075-179248075
GRCh38: 5:179821075-179821075
31 SQSTM1 NM_003900.5(SQSTM1):c.626G>A (p.Arg209His) SNV Uncertain significance 838159 GRCh37: 5:179251276-179251276
GRCh38: 5:179824276-179824276
32 SQSTM1 NM_003900.5(SQSTM1):c.241G>A (p.Glu81Lys) SNV Uncertain significance 838847 GRCh37: 5:179249993-179249993
GRCh38: 5:179822993-179822993
33 SQSTM1 NM_003900.5(SQSTM1):c.374A>G (p.Asn125Ser) SNV Uncertain significance 839604 GRCh37: 5:179250930-179250930
GRCh38: 5:179823930-179823930
34 SQSTM1 NM_003900.5(SQSTM1):c.767A>G (p.Asp256Gly) SNV Uncertain significance 850973 GRCh37: 5:179260044-179260044
GRCh38: 5:179833044-179833044
35 SQSTM1 NM_003900.5(SQSTM1):c.756C>T (p.Gly252=) SNV Uncertain significance 388956 rs769297000 GRCh37: 5:179260033-179260033
GRCh38: 5:179833033-179833033
36 SQSTM1 NM_003900.5(SQSTM1):c.1316C>T (p.Pro439Leu) SNV Uncertain significance 851619 GRCh37: 5:179263586-179263586
GRCh38: 5:179836586-179836586
37 SQSTM1 NM_003900.5(SQSTM1):c.5C>T (p.Ala2Val) SNV Uncertain significance 861123 GRCh37: 5:179247941-179247941
GRCh38: 5:179820941-179820941
38 SQSTM1 NM_003900.5(SQSTM1):c.1313C>T (p.Pro438Leu) SNV Uncertain significance 947710 GRCh37: 5:179263583-179263583
GRCh38: 5:179836583-179836583
39 SQSTM1 NM_003900.5(SQSTM1):c.827C>T (p.Ser276Phe) SNV Uncertain significance 955638 GRCh37: 5:179260104-179260104
GRCh38: 5:179833104-179833104
40 SQSTM1 NM_003900.5(SQSTM1):c.121C>T (p.Pro41Ser) SNV Uncertain significance 959506 GRCh37: 5:179248057-179248057
GRCh38: 5:179821057-179821057
41 SQSTM1 NM_003900.5(SQSTM1):c.1166-1G>A SNV Uncertain significance 962371 GRCh37: 5:179263435-179263435
GRCh38: 5:179836435-179836435
42 SQSTM1 NM_003900.5(SQSTM1):c.50C>T (p.Ala17Val) SNV Uncertain significance 906314 GRCh37: 5:179247986-179247986
GRCh38: 5:179820986-179820986
43 SQSTM1 NM_003900.5(SQSTM1):c.1032A>G (p.Lys344=) SNV Uncertain significance 969428 GRCh37: 5:179260649-179260649
GRCh38: 5:179833649-179833649
44 TNFRSF11A NM_003839.4(TNFRSF11A):c.284-4G>A SNV Uncertain significance 891049 GRCh37: 18:60021620-60021620
GRCh38: 18:62354387-62354387
45 TNFRSF11A NM_003839.4(TNFRSF11A):c.133C>T (p.Arg45Trp) SNV Uncertain significance 891048 GRCh37: 18:60015458-60015458
GRCh38: 18:62348225-62348225
46 SQSTM1 NM_003900.5(SQSTM1):c.695C>T (p.Pro232Leu) SNV Uncertain significance 969651 GRCh37: 5:179252167-179252167
GRCh38: 5:179825167-179825167
47 TNFRSF11A NM_003839.4(TNFRSF11A):c.-22G>T SNV Uncertain significance 888782 GRCh37: 18:59992564-59992564
GRCh38: 18:62325331-62325331
48 TNFRSF11A NM_003839.4(TNFRSF11A):c.1254T>G (p.Ser418=) SNV Uncertain significance 287597 rs34966542 GRCh37: 18:60036404-60036404
GRCh38: 18:62369171-62369171
49 TNFRSF11A NM_003839.4(TNFRSF11A):c.1279G>A (p.Asp427Asn) SNV Uncertain significance 713429 rs201402594 GRCh37: 18:60036429-60036429
GRCh38: 18:62369196-62369196
50 TNFRSF11A NM_003839.4(TNFRSF11A):c.*126C>T SNV Uncertain significance 892431 GRCh37: 18:60052393-60052393
GRCh38: 18:62385160-62385160

Expression for Paget Disease of Bone 2, Early-Onset

Search GEO for disease gene expression data for Paget Disease of Bone 2, Early-Onset.

Pathways for Paget Disease of Bone 2, Early-Onset

Pathways related to Paget Disease of Bone 2, Early-Onset according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.55 TNFRSF11A SQSTM1
2 11.06 TNFRSF11A SQSTM1
3
Show member pathways
10.49 TNFRSF11A SQSTM1

GO Terms for Paget Disease of Bone 2, Early-Onset

Sources for Paget Disease of Bone 2, Early-Onset

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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