PDB2
MCID: PGT009
MIFTS: 36

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
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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 73 28 5
Pdb2 57 73
Paget Disease of Bone, Type 2, Early-Onset 38

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable severity
progressive disorder
onset in teens or early twenties


HPO:

30
paget disease of bone 2, early-onset:
Onset and clinical course progressive


Classifications:



Summaries for Paget Disease of Bone 2, Early-Onset

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 08-Dec-2022)

MalaCards based summary: Paget Disease of Bone 2, Early-Onset, also known as pdb2, is related to paget's disease of bone and mammary paget's disease. 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 Cytokine Signaling in Immune system and Clock-controlled autophagy in bone metabolism. Affiliated tissues include bone and brain, and related phenotypes are hypercalcemia and headache

UniProtKB/Swiss-Prot: 73 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.

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 paget's disease of bone 30.9 TNFRSF11A SQSTM1
2 mammary paget's disease 29.4 TNFRSF11A SQSTM1
3 paget disease of bone 3 10.0
4 osteogenic sarcoma 10.0
5 periostitis 9.7 TNFRSF11A SQSTM1
6 familial expansile osteolysis 9.7 TNFRSF11A SQSTM1
7 breast adenocarcinoma 9.5 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:

30 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypercalcemia 30 Very rare (1%) HP:0003072
2 headache 30 Very rare (1%) HP:0002315
3 femoral bowing 30 Very rare (1%) HP:0002980
4 increased susceptibility to fractures 30 Very rare (1%) HP:0002659
5 short femur 30 Very rare (1%) HP:0003097
6 bilateral conductive hearing impairment 30 Very rare (1%) HP:0008513
7 sclerosis of skull base 30 Very rare (1%) HP:0002694
8 sandwich appearance of vertebral bodies 30 Very rare (1%) HP:0004618
9 elevated circulating alkaline phosphatase concentration 30 Very rare (1%) HP:0003155
10 osteosclerosis of the ulna 30 Very rare (1%) HP:0003991
11 bowing of the long bones 30 HP:0006487
12 cranial nerve paralysis 30 HP:0006824
13 bone pain 30 HP:0002653
14 osteolysis 30 HP:0002797
15 brain stem compression 30 HP:0002512
16 fractures of the long bones 30 HP:0003084
17 tetraparesis 30 HP:0002273
18 premature loss of teeth 30 HP:0006480
19 paraparesis 30 HP:0002385
20 hydroxyprolinuria 30 HP:0003080
21 long-tract signs 30 HP:0002423
22 vertebral compression fracture 30 HP:0002953

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 08-Dec-2022)

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 28 TNFRSF11A

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

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

MalaCards : 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. 57 5
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 5
11771666 2002
3
Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. 57 5
10615125 2000
4
Beyond dystonia and ataxia: Expanding the phenotype of SQSTM1 mutations. 5
30638816 2019
5
Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration. 5
29959261 2018
6
Absence of the Autophagy Adaptor SQSTM1/p62 Causes Childhood-Onset Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy. 5
27545679 2016
7
Targeted next-generation sequencing assay for detection of mutations in primary myopathies. 5
26627873 2016
8
Selective autophagic receptor p62 regulates the abundance of transcriptional coregulator ARIP4 during nutrient starvation. 5
26412716 2015
9
SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles. 5
26208961 2015
10
Genetics of Paget's disease of bone. 57
24988994 2014
11
Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. 5
23417734 2013
12
SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. 5
22084127 2011
13
Pathogenesis and management of Paget's disease of bone. 57
18620951 2008
14
Delayed development of Paget's disease in offspring inheriting SQSTM1 mutations. 5
17181397 2007
15
Paget's disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations. 5
17129171 2007
16
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. 5
17576681 2007
17
Identification and molecular characterization of a novel splice-site mutation (G1205C) in the SQSTM1 gene causing Paget's disease of bone in an extended American family. 5
17120186 2006
18
Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences. 5
15176995 2004
19
Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. 57
12929927 2003
20
Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease. 5
12374763 2002
21
Paget's disease of bone: evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneity. 57
9626621 1998
22
Statistical features of human exons and their flanking regions. 5
9536098 1998
23
Genetic linkage of Paget disease of the bone to chromosome 18q. 57
9345096 1997
24
Achieving Molecular Fluorescent Conversion from Aggregation-Caused Quenching to Aggregation-Induced Emission by Positional Isomerization. 62
35011426 2021
25
Early-onset Paget's disease of bone in a Mexican family caused by a novel tandem duplication (77dup27) in TNFRSF11A that encodes RANK. 62
31923705 2020
26
Robust DNase activity of the ooplasm can act as a gametic transfection barrier in rainbow trout. 62
31574402 2020
27
Isolation, characterization and growth kinetics of phenol hyper-tolerant bacteria from sewage-fed aquaculture system. 62
31790335 2020
28
Dysosteosclerosis is also caused by TNFRSF11A mutation. 62
29568001 2018
29
Developing a puncture-free in ovo chicken transfection strategy based on bypassing albumen nucleases. 62
28215692 2017
30
Evidence of circulation of the novel border disease virus genotype 8 in chamois. 62
27761745 2017
31
Constructing a Mouse Oct4 Promoter/EGFP Vector, as a Whole-Cellular Reporter to Monitor the Pluripotent State of Cells. 62
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. 62
17284635 2007
33
Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling. 62
16831914 2006
34
Heritable disorders of the RANKL/OPG/RANK signaling pathway. 62
15615493 2004
35
Linkage of Paget disease of bone to a novel region on human chromosome 18q23. 62
11742440 2002
36
Paget disease of bone: mapping of two loci at 5q35-qter and 5q31. 62
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. 62
11149487 2001
38
Citrate synthase activity in Escherichia coli harbouring hybrid plasmids containing the gltA gene. 62
6355385 1983

Variations for Paget Disease of Bone 2, Early-Onset

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

5 (show top 50) (show all 453)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TNFRSF11A NM_003839.4(TNFRSF11A):c.49_63dup (p.Leu17_Leu21dup) DUP Pathogenic
208144 rs1555767678 GRCh37: 18:59992633-59992634
GRCh38: 18:62325400-62325401
2 SQSTM1 NM_003900.5(SQSTM1):c.1054G>T (p.Glu352Ter) SNV Pathogenic
1319146 GRCh37: 5:179260671-179260671
GRCh38: 5:179833671-179833671
3 SQSTM1 NM_003900.5(SQSTM1):c.301+1G>T SNV Pathogenic
1387627 GRCh37: 5:179250054-179250054
GRCh38: 5:179823054-179823054
4 SQSTM1 NM_003900.5(SQSTM1):c.1231G>A (p.Gly411Ser) SNV Pathogenic
1458052 GRCh37: 5:179263501-179263501
GRCh38: 5:179836501-179836501
5 SQSTM1 NM_003900.5(SQSTM1):c.244G>T (p.Glu82Ter) SNV Pathogenic
1076912 GRCh37: 5:179249996-179249996
GRCh38: 5:179822996-179822996
6 SQSTM1 NM_003900.5(SQSTM1):c.1165G>C (p.Glu389Gln) SNV Pathogenic
1459183 GRCh37: 5:179260782-179260782
GRCh38: 5:179833782-179833782
7 SQSTM1 NM_003900.5(SQSTM1):c.995C>G (p.Ser332Ter) SNV Pathogenic
642133 rs1185406298 GRCh37: 5:179260612-179260612
GRCh38: 5:179833612-179833612
8 SQSTM1 NM_003900.5(SQSTM1):c.526_529del (p.Ser176fs) DEL Pathogenic
503881 rs1331685476 GRCh37: 5:179251079-179251082
GRCh38: 5:179824079-179824082
9 SQSTM1 NM_003900.5(SQSTM1):c.810del (p.Val271fs) DEL Pathogenic
967349 rs1758316662 GRCh37: 5:179260083-179260083
GRCh38: 5:179833083-179833083
10 TNFRSF11A NM_003839.4(TNFRSF11A):c.39_65dup (p.Leu14_Ala22dup) DUP Pathogenic
6300 rs796051862 GRCh37: 18:59992619-59992620
GRCh38: 18:62325386-62325387
11 SQSTM1 NM_003900.5(SQSTM1):c.1185dup (p.Glu396Ter) DUP Pathogenic
835699 rs1254158201 GRCh37: 5:179263453-179263454
GRCh38: 5:179836453-179836454
12 TNFRSF11A NM_003839.4(TNFRSF11A):c.45_62dup (p.Leu16_Leu21dup) DUP Pathogenic
208143 rs886037749 GRCh37: 18:59992620-59992621
GRCh38: 18:62325387-62325388
13 SQSTM1 NM_003900.5(SQSTM1):c.1211T>C (p.Met404Thr) SNV Pathogenic
855037 rs1247551175 GRCh37: 5:179263481-179263481
GRCh38: 5:179836481-179836481
14 SQSTM1 NM_003900.5(SQSTM1):c.286C>T (p.Arg96Ter) SNV Pathogenic
265782 rs886039782 GRCh37: 5:179250038-179250038
GRCh38: 5:179823038-179823038
15 SQSTM1 NM_003900.5(SQSTM1):c.1170del (p.Asp391fs) DEL Pathogenic
1069495 GRCh37: 5:179263440-179263440
GRCh38: 5:179836440-179836440
16 SQSTM1 NM_003900.5(SQSTM1):c.1210A>G (p.Met404Val) SNV Pathogenic
1071292 GRCh37: 5:179263480-179263480
GRCh38: 5:179836480-179836480
17 SQSTM1 NM_003900.5(SQSTM1):c.1273G>A (p.Gly425Arg) SNV Pathogenic
1163456 GRCh37: 5:179263543-179263543
GRCh38: 5:179836543-179836543
18 SQSTM1 NM_003900.5(SQSTM1):c.1165+1G>A SNV Pathogenic
8110 rs796051870 GRCh37: 5:179260783-179260783
GRCh38: 5:179833783-179833783
19 SQSTM1 NM_003900.5(SQSTM1):c.970-2A>G SNV Likely Pathogenic
1473565 GRCh37: 5:179260585-179260585
GRCh38: 5:179833585-179833585
20 SQSTM1 NC_000005.9:g.(?_179260012)_(179260802_?)del DEL Uncertain Significance
1448318 GRCh37: 5:179260012-179260802
GRCh38:
21 SQSTM1 NM_003900.5(SQSTM1):c.557G>A (p.Arg186Gln) SNV Uncertain Significance
1448375 GRCh37: 5:179251207-179251207
GRCh38: 5:179824207-179824207
22 SQSTM1 NM_003900.5(SQSTM1):c.964C>T (p.Pro322Ser) SNV Uncertain Significance
1433383 GRCh37: 5:179260241-179260241
GRCh38: 5:179833241-179833241
23 SQSTM1 NM_003900.5(SQSTM1):c.385G>T (p.Asp129Tyr) SNV Uncertain Significance
1493743 GRCh37: 5:179250941-179250941
GRCh38: 5:179823941-179823941
24 SQSTM1 NM_003900.5(SQSTM1):c.771C>G (p.Ile257Met) SNV Uncertain Significance
1494010 GRCh37: 5:179260048-179260048
GRCh38: 5:179833048-179833048
25 SQSTM1 NM_003900.5(SQSTM1):c.1276G>A (p.Ala426Thr) SNV Uncertain Significance
1436054 GRCh37: 5:179263546-179263546
GRCh38: 5:179836546-179836546
26 SQSTM1 NM_003900.5(SQSTM1):c.998G>A (p.Gly333Glu) SNV Uncertain Significance
1468320 GRCh37: 5:179260615-179260615
GRCh38: 5:179833615-179833615
27 SQSTM1 NM_003900.5(SQSTM1):c.634C>G (p.Arg212Gly) SNV Uncertain Significance
1483836 GRCh37: 5:179251284-179251284
GRCh38: 5:179824284-179824284
28 SQSTM1 NM_003900.5(SQSTM1):c.1069C>G (p.Gln357Glu) SNV Uncertain Significance
1498798 GRCh37: 5:179260686-179260686
GRCh38: 5:179833686-179833686
29 SQSTM1 NM_003900.5(SQSTM1):c.319C>T (p.Arg107Trp) SNV Uncertain Significance
1449965 GRCh37: 5:179250875-179250875
GRCh38: 5:179823875-179823875
30 SQSTM1 NM_003900.5(SQSTM1):c.703A>G (p.Asn235Asp) SNV Uncertain Significance
1476497 GRCh37: 5:179252175-179252175
GRCh38: 5:179825175-179825175
31 SQSTM1 NM_003900.5(SQSTM1):c.173_175del (p.Leu58del) DEL Uncertain Significance
1511548 GRCh37: 5:179248107-179248109
GRCh38: 5:179821107-179821109
32 SQSTM1 NM_003900.5(SQSTM1):c.1109C>T (p.Ser370Phe) SNV Uncertain Significance
1497467 GRCh37: 5:179260726-179260726
GRCh38: 5:179833726-179833726
33 SQSTM1 NM_003900.5(SQSTM1):c.575A>G (p.His192Arg) SNV Uncertain Significance
1521767 GRCh37: 5:179251225-179251225
GRCh38: 5:179824225-179824225
34 SQSTM1 NM_003900.5(SQSTM1):c.847A>G (p.Ser283Gly) SNV Uncertain Significance
1498386 GRCh37: 5:179260124-179260124
GRCh38: 5:179833124-179833124
35 SQSTM1 NM_003900.5(SQSTM1):c.907G>A (p.Ala303Thr) SNV Uncertain Significance
1351752 GRCh37: 5:179260184-179260184
GRCh38: 5:179833184-179833184
36 SQSTM1 NM_003900.5(SQSTM1):c.527C>G (p.Ser176Cys) SNV Uncertain Significance
1418751 GRCh37: 5:179251083-179251083
GRCh38: 5:179824083-179824083
37 SQSTM1 NM_003900.5(SQSTM1):c.274G>A (p.Asp92Asn) SNV Uncertain Significance
1442932 GRCh37: 5:179250026-179250026
GRCh38: 5:179823026-179823026
38 SQSTM1 NM_003900.5(SQSTM1):c.622C>A (p.Pro208Thr) SNV Uncertain Significance
1461746 GRCh37: 5:179251272-179251272
GRCh38: 5:179824272-179824272
39 SQSTM1 NM_003900.5(SQSTM1):c.634C>T (p.Arg212Cys) SNV Uncertain Significance
1439801 GRCh37: 5:179251284-179251284
GRCh38: 5:179824284-179824284
40 SQSTM1 NM_003900.4(SQSTM1):c.970del DEL Uncertain Significance
542159 rs758377403 GRCh37: 5:179260586-179260586
GRCh38: 5:179833586-179833586
41 SQSTM1 NM_003900.5(SQSTM1):c.1160C>T (p.Pro387Leu) SNV Uncertain Significance
202211 rs776749939 GRCh37: 5:179260777-179260777
GRCh38: 5:179833777-179833777
42 SQSTM1 NM_003900.5(SQSTM1):c.769A>G (p.Ile257Val) SNV Uncertain Significance
1392396 GRCh37: 5:179260046-179260046
GRCh38: 5:179833046-179833046
43 TNFRSF11A NM_003839.4(TNFRSF11A):c.1018T>A (p.Phe340Ile) SNV Uncertain Significance
891182 rs764498229 GRCh37: 18:60036168-60036168
GRCh38: 18:62368935-62368935
44 TNFRSF11A NM_003839.4(TNFRSF11A):c.1618A>G (p.Met540Val) SNV Uncertain Significance
327738 rs117028614 GRCh37: 18:60052034-60052034
GRCh38: 18:62384801-62384801
45 SQSTM1 NM_003900.5(SQSTM1):c.698G>C (p.Ser233Thr) SNV Uncertain Significance
1717299 GRCh37: 5:179252170-179252170
GRCh38: 5:179825170-179825170
46 SQSTM1 NM_003900.5(SQSTM1):c.104C>G (p.Ala35Gly) SNV Uncertain Significance
1713579 GRCh37: 5:179248040-179248040
GRCh38: 5:179821040-179821040
47 SQSTM1 NM_003900.5(SQSTM1):c.1104C>A (p.Asp368Glu) SNV Uncertain Significance
1719509 GRCh37: 5:179260721-179260721
GRCh38: 5:179833721-179833721
48 SQSTM1 NM_003900.5(SQSTM1):c.1198C>A (p.Gln400Lys) SNV Uncertain Significance
1719645 GRCh37: 5:179263468-179263468
GRCh38: 5:179836468-179836468
49 SQSTM1 NM_003900.5(SQSTM1):c.3G>A (p.Met1Ile) SNV Uncertain Significance
1472643 GRCh37: 5:179247939-179247939
GRCh38: 5:179820939-179820939
50 SQSTM1 NM_003900.5(SQSTM1):c.1288A>C (p.Thr430Pro) SNV Uncertain Significance
1434014 GRCh37: 5:179263558-179263558
GRCh38: 5:179836558-179836558

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
12.24 TNFRSF11A SQSTM1
2 10.86 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

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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