MCID: PGT009
MIFTS: 24

Paget Disease of Bone 2, Early-Onset

Categories: Genetic diseases, Bone 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 75 29 6
Pdb2 57 75
Paget Disease of Bone, Type 2, Early-Onset 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
paget disease of bone 2, early-onset:
Onset and clinical course variable expressivity progressive
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Paget Disease of Bone 2, Early-Onset

UniProtKB/Swiss-Prot : 75 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 paget's disease of bone and familial expansile osteolysis. 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 tetraparesis and paraparesis

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)

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

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 28.4 SQSTM1 TNFRSF11A
2 familial expansile osteolysis 9.3 SQSTM1 TNFRSF11A
3 periostitis 9.2 SQSTM1 TNFRSF11A

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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 tetraparesis 32 HP:0002273
2 paraparesis 32 HP:0002385
3 long-tract signs 32 HP:0002423
4 brain stem compression 32 HP:0002512
5 abnormality of pelvic girdle bone morphology 32 HP:0002644
6 bone pain 32 HP:0002653
7 increased susceptibility to fractures 32 HP:0002659
8 osteolysis 32 HP:0002797
9 vertebral compression fractures 32 HP:0002953
10 hydroxyprolinuria 32 HP:0003080
11 fractures of the long bones 32 HP:0003084
12 elevated alkaline phosphatase 32 HP:0003155
13 premature loss of teeth 32 HP:0006480
14 cranial nerve paralysis 32 HP:0006824
15 bilateral conductive hearing impairment 32 very rare (1%) HP:0008513

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 SQSTM1 TNFRSF11A

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

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

41
Bone, Brain

Publications for Paget Disease of Bone 2, Early-Onset

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 88)
# Gene Variation Type Significance SNP ID Assembly Location
1 TNFRSF11A NM_003839.3(TNFRSF11A) duplication Pathogenic rs796051862 GRCh38 Chromosome 18, 62325391: 62325417
2 TNFRSF11A NM_003839.3(TNFRSF11A) duplication Pathogenic rs796051862 GRCh37 Chromosome 18, 59992624: 59992650
3 SQSTM1 NM_003900.4(SQSTM1): c.970_1165del single nucleotide variant Pathogenic rs796051870 GRCh38 Chromosome 5, 179833783: 179833783
4 SQSTM1 NM_003900.4(SQSTM1): c.970_1165del single nucleotide variant Pathogenic rs796051870 GRCh37 Chromosome 5, 179260783: 179260783
5 TNFRSF11A NM_003839.3(TNFRSF11A): c.49_63dupCTCTGCGCGCTGCTC (p.Leu21_Ala22insLeuCysAlaLeuLeu) duplication Pathogenic rs879253796 GRCh38 Chromosome 18, 62325401: 62325415
6 TNFRSF11A NM_003839.3(TNFRSF11A): c.49_63dupCTCTGCGCGCTGCTC (p.Leu21_Ala22insLeuCysAlaLeuLeu) duplication Pathogenic rs879253796 GRCh37 Chromosome 18, 59992634: 59992648
7 SQSTM1 NM_001142298.1(SQSTM1): c.-47-1924C> T single nucleotide variant Likely benign rs200396166 GRCh38 Chromosome 5, 179821034: 179821034
8 SQSTM1 NM_001142298.1(SQSTM1): c.-47-1924C> T single nucleotide variant Likely benign rs200396166 GRCh37 Chromosome 5, 179248034: 179248034
9 SQSTM1 NM_003900.4(SQSTM1): c.822G> C (p.Glu274Asp) single nucleotide variant Benign/Likely benign rs55793208 GRCh37 Chromosome 5, 179260099: 179260099
10 SQSTM1 NM_003900.4(SQSTM1): c.822G> C (p.Glu274Asp) single nucleotide variant Benign/Likely benign rs55793208 GRCh38 Chromosome 5, 179833099: 179833099
11 SQSTM1 NM_003900.4(SQSTM1): c.876C> T (p.Asp292=) single nucleotide variant Benign/Likely benign rs4935 GRCh37 Chromosome 5, 179260153: 179260153
12 SQSTM1 NM_003900.4(SQSTM1): c.876C> T (p.Asp292=) single nucleotide variant Benign/Likely benign rs4935 GRCh38 Chromosome 5, 179833153: 179833153
13 SQSTM1 NM_003900.4(SQSTM1): c.924G> A (p.Ala308=) single nucleotide variant Likely benign rs139482113 GRCh37 Chromosome 5, 179260201: 179260201
14 SQSTM1 NM_003900.4(SQSTM1): c.924G> A (p.Ala308=) single nucleotide variant Likely benign rs139482113 GRCh38 Chromosome 5, 179833201: 179833201
15 SQSTM1 NM_003900.4(SQSTM1): c.936G> A (p.Arg312=) single nucleotide variant Benign/Likely benign rs4797 GRCh37 Chromosome 5, 179260213: 179260213
16 SQSTM1 NM_003900.4(SQSTM1): c.936G> A (p.Arg312=) single nucleotide variant Benign/Likely benign rs4797 GRCh38 Chromosome 5, 179833213: 179833213
17 SQSTM1 NM_003900.4(SQSTM1): c.954C> T (p.Ser318=) single nucleotide variant Benign/Likely benign rs56092424 GRCh37 Chromosome 5, 179260231: 179260231
18 SQSTM1 NM_003900.4(SQSTM1): c.954C> T (p.Ser318=) single nucleotide variant Benign/Likely benign rs56092424 GRCh38 Chromosome 5, 179833231: 179833231
19 SQSTM1 NM_003900.4(SQSTM1): c.961C> T (p.Arg321Cys) single nucleotide variant Benign/Likely benign rs140226523 GRCh37 Chromosome 5, 179260238: 179260238
20 SQSTM1 NM_003900.4(SQSTM1): c.961C> T (p.Arg321Cys) single nucleotide variant Benign/Likely benign rs140226523 GRCh38 Chromosome 5, 179833238: 179833238
21 SQSTM1 NM_003900.4(SQSTM1): c.1044G> A (p.Pro348=) single nucleotide variant Benign/Likely benign rs10058037 GRCh37 Chromosome 5, 179260661: 179260661
22 SQSTM1 NM_003900.4(SQSTM1): c.1044G> A (p.Pro348=) single nucleotide variant Benign/Likely benign rs10058037 GRCh38 Chromosome 5, 179833661: 179833661
23 SQSTM1 NM_003900.4(SQSTM1): c.819A> G (p.Pro273=) single nucleotide variant Conflicting interpretations of pathogenicity rs200388590 GRCh38 Chromosome 5, 179833096: 179833096
24 SQSTM1 NM_003900.4(SQSTM1): c.819A> G (p.Pro273=) single nucleotide variant Conflicting interpretations of pathogenicity rs200388590 GRCh37 Chromosome 5, 179260096: 179260096
25 SQSTM1 NM_003900.4(SQSTM1): c.955G> A (p.Glu319Lys) single nucleotide variant Benign/Likely benign rs61748794 GRCh37 Chromosome 5, 179260232: 179260232
26 SQSTM1 NM_003900.4(SQSTM1): c.955G> A (p.Glu319Lys) single nucleotide variant Benign/Likely benign rs61748794 GRCh38 Chromosome 5, 179833232: 179833232
27 SQSTM1 NM_003900.4(SQSTM1): c.183C> T (p.Gly61=) single nucleotide variant Benign/Likely benign rs767340839 GRCh38 Chromosome 5, 179821119: 179821119
28 SQSTM1 NM_003900.4(SQSTM1): c.183C> T (p.Gly61=) single nucleotide variant Benign/Likely benign rs767340839 GRCh37 Chromosome 5, 179248119: 179248119
29 SQSTM1 NM_003900.4(SQSTM1): c.612A> G (p.Gly204=) single nucleotide variant Conflicting interpretations of pathogenicity rs878982215 GRCh38 Chromosome 5, 179824262: 179824262
30 SQSTM1 NM_003900.4(SQSTM1): c.612A> G (p.Gly204=) single nucleotide variant Conflicting interpretations of pathogenicity rs878982215 GRCh37 Chromosome 5, 179251262: 179251262
31 SQSTM1 NM_003900.4(SQSTM1): c.1230C> T (p.Gly410=) single nucleotide variant Likely benign rs766437927 GRCh37 Chromosome 5, 179263500: 179263500
32 SQSTM1 NM_003900.4(SQSTM1): c.1230C> T (p.Gly410=) single nucleotide variant Likely benign rs766437927 GRCh38 Chromosome 5, 179836500: 179836500
33 SQSTM1 NM_003900.4(SQSTM1): c.46G> A (p.Ala16Thr) single nucleotide variant Uncertain significance rs773552098 GRCh38 Chromosome 5, 179820982: 179820982
34 SQSTM1 NM_003900.4(SQSTM1): c.46G> A (p.Ala16Thr) single nucleotide variant Uncertain significance rs773552098 GRCh37 Chromosome 5, 179247982: 179247982
35 SQSTM1 NM_003900.4(SQSTM1): c.996A> G (p.Ser332=) single nucleotide variant Benign/Likely benign rs141436407 GRCh38 Chromosome 5, 179833613: 179833613
36 SQSTM1 NM_003900.4(SQSTM1): c.996A> G (p.Ser332=) single nucleotide variant Benign/Likely benign rs141436407 GRCh37 Chromosome 5, 179260613: 179260613
37 SQSTM1 NM_003900.4(SQSTM1): c.268G> A (p.Val90Met) single nucleotide variant Uncertain significance rs181263868 GRCh37 Chromosome 5, 179250020: 179250020
38 SQSTM1 NM_003900.4(SQSTM1): c.268G> A (p.Val90Met) single nucleotide variant Uncertain significance rs181263868 GRCh38 Chromosome 5, 179823020: 179823020
39 SQSTM1 NM_003900.4(SQSTM1): c.317G> A (p.Arg106Gln) single nucleotide variant Uncertain significance rs778554903 GRCh38 Chromosome 5, 179823873: 179823873
40 SQSTM1 NM_003900.4(SQSTM1): c.317G> A (p.Arg106Gln) single nucleotide variant Uncertain significance rs778554903 GRCh37 Chromosome 5, 179250873: 179250873
41 SQSTM1 NM_003900.4(SQSTM1): c.888G> A (p.Pro296=) single nucleotide variant Benign rs148984239 GRCh38 Chromosome 5, 179833165: 179833165
42 SQSTM1 NM_003900.4(SQSTM1): c.888G> A (p.Pro296=) single nucleotide variant Benign rs148984239 GRCh37 Chromosome 5, 179260165: 179260165
43 SQSTM1 NM_003900.4(SQSTM1): c.1178G> A (p.Arg393Gln) single nucleotide variant Uncertain significance rs200551825 GRCh37 Chromosome 5, 179263448: 179263448
44 SQSTM1 NM_003900.4(SQSTM1): c.1178G> A (p.Arg393Gln) single nucleotide variant Uncertain significance rs200551825 GRCh38 Chromosome 5, 179836448: 179836448
45 SQSTM1 NM_003900.4(SQSTM1): c.332C> T (p.Pro111Leu) single nucleotide variant Uncertain significance rs371719657 GRCh37 Chromosome 5, 179250888: 179250888
46 SQSTM1 NM_003900.4(SQSTM1): c.332C> T (p.Pro111Leu) single nucleotide variant Uncertain significance rs371719657 GRCh38 Chromosome 5, 179823888: 179823888
47 SQSTM1 NM_003900.4(SQSTM1): c.763G> C (p.Val255Leu) single nucleotide variant Uncertain significance rs182522590 GRCh38 Chromosome 5, 179833040: 179833040
48 SQSTM1 NM_003900.4(SQSTM1): c.763G> C (p.Val255Leu) single nucleotide variant Uncertain significance rs182522590 GRCh37 Chromosome 5, 179260040: 179260040
49 SQSTM1 NM_003900.4(SQSTM1): c.800G> A (p.Arg267His) single nucleotide variant Uncertain significance rs149424705 GRCh37 Chromosome 5, 179260077: 179260077
50 SQSTM1 NM_003900.4(SQSTM1): c.800G> A (p.Arg267His) single nucleotide variant Uncertain significance rs149424705 GRCh38 Chromosome 5, 179833077: 179833077

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

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

Sources for Paget Disease of Bone 2, Early-Onset

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