|
TNFRSF11A
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Recessive, loss-of-function mutations in the TNFRSF11B gene, which encodes osteoprotegerin, cause juvenile PDB and here the bone disease is due to unopposed activation of RANK by RANKL.
|
30756140 |
2019 |
|
TNFRSF11A
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
RANK ligand (RANKL), a critical osteoclastogenic factor expressed on bone marrow stromal/preosteoblast cells is upregulated in PDB.
|
23553658 |
2013 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Here, we identified two nonsynonymous single nucleotide polymorphisms (SNPs) (C421T, H141Y and T575C, V192A) in the TNFRSF11A gene, associated with PDB and with the severity of phenotype in a large population of 654 unrelated patients that were previously screened for SQSTM1 gene mutations.
|
21987421 |
2012 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
However, PDB patients without SQSTM1 mutations seem to have susceptibility genetic polymorphisms in regions containing the CaSR, ESR1, TNFRSF11B (OPG), TNFRSF11A (RANK), CSF1 (M-CSF), OPTN, TM7SF4 (DC-STAMP), VCP, NUP205, RIN3, PML, and GOLGA6A genes, resulting in an increased risk of developing PDB.
|
21959292 |
2012 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study.
|
21623375 |
2011 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone.
|
20436471 |
2010 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The majority of the genetic risk for Paget's disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes.
|
20839008 |
2010 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
To investigate the possible relationship between TNFRSF11A polymorphisms and sporadic PDB, we conducted an association study including 32 single-nucleotide polymorphisms (SNPs) in 196 Belgian sporadic PDB patients and 212 control individuals.
|
20564239 |
2010 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
CTD_human |
These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility.
|
20436471 |
2010 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the TNFRSF11A gene in a Chinese family.
|
19578385 |
2009 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Earlier-onset conditions with similar bone pathology (familial expansile osteolysis, expansile skeletal hyperphosphatasia and early-onset PDB) are caused by mutations in TNFRSF11A (RANK).
|
18359282 |
2008 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Clinical and biochemical response of TNFRSF11A-mediated early-onset familial Paget disease to bisphosphonate therapy.
|
18836673 |
2008 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Whilst the disease mechanism in these cases is likely to involve aberrant RANK-mediated osteoclast NF-kappaB signalling, the precise relationship between other potential contributors, such as viruses and environmental factors, and the molecular pathogenesis of PDB is less clear.
|
17903332 |
2007 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Modulation of the osteoclast RANK-NF-kappaB signalling axis may represent a viable therapeutic strategy for Paget's disease and other conditions where excessive bone resorption or remodelling is a feature.
|
18047742 |
2007 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
To further clarify the functional impact of p62 mutations associated with PDB, we assessed the effect of p62 mutation (a novel mutation: K378X, and previously reported mutations: P392L and E396X) on RANK-induced NF-kappaB activation and compared this with the effect of wildtype p62.
|
16813535 |
2006 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Osteoclasts and osteoclast precursors from patients with Paget's disease contain paramyxoviral transcripts and appear hyperresponsive to 1,25-(OH)2D3 and RANK ligand (RANKL).
|
15389972 |
2004 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Previous analysis of tumor-specific constitutional LOH had identified a putative tumor-suppressor gene (LOH18CR) active in osteosarcoma tumorigenesis, which mapped to a subregion of chromosome 18q linked to both familial Paget's disease and FEO.
|
12673693 |
2003 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
We conclude that the 75dup27 mutation of RANK causes a Paget's disease of bone-like phenotype that is distinct from, but which overlaps with, FEO and ESH.
|
12929927 |
2003 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Previous analysis of tumor-specific constitutional LOH had identified a putative tumor-suppressor gene (LOH18CR) active in osteosarcoma tumorigenesis, which mapped to a subregion of chromosome 18q linked to both familial Paget's disease and FEO.
|
12673693 |
2003 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
We have excluded linkage, both to PDB1 and to PDB2, in a large multigenerational pedigree with multiple family members affected by PDB.
|
11742440 |
2002 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees.
|
11149487 |
2001 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
In order to investigate the possible role of TNFRSF11A in the pathogenesis of Paget's disease and osteosarcoma, we conducted mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in Pagetic bone and six osteosarcoma cell lines.
|
11351498 |
2001 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma.
|
11351498 |
2001 |
|
TNFRSF11A
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Recently, mutations in the RANK gene have been shown to cause familial expansile osteolysis, a rare bone disorder showing great similarity to PDB.
|
11165949 |
2001 |
|
TNFRSF11A
|
0.600 |
Biomarker
|
disease |
BEFREE |
Genetic factors are important in the pathogenesis of PDB, and previous studies have shown that the PDB-like bone dysplasia familial expansile osteolysis is caused by activating mutations in the TNFRSF11A gene that encodes receptor activator of nuclear factor kappa B (RANK); however, linkage studies, coupled with mutation screening, have excluded involvement of RANK in the vast majority of patients with PDB.
|
11555792 |
2001 |