|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
It is now clear that PDB is a genetically heterogeneous disorder, with mutations in at least two different genes (SQSTM1, ZNF687) and more common predisposing variants.
|
30671590 |
2019 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
Hepatosplenomegaly, pneumopathy, bone changes and fronto-temporal dementia: Niemann-Pick type B and SQSTM1-associated Paget's disease in the same individual.
|
29948344 |
2019 |
|
Osteitis Deformans
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
SQSTM1 gene expression was upregulated in osteoclasts from patients with PDB versus healthy controls in presence of cadmium, and SQSTM1 protein expression was upregulated in presence of bismuth and tobacco smoke condensates, in particular in osteoclasts from carriers of the SQSTM1 mutation.
|
30594595 |
2019 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Mutations in sequestosome-1 (<i>SQSTM1</i>) are strongly associated with the development of PDB.
|
31488492 |
2019 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
The incidence of new Paget's disease in SQSTM1 positive subjects was 7.1% and no mutation-negative subject developed the disease within 16 years of follow-up.
|
31449886 |
2019 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Direct sequencing of ancient DNA excluded contemporary PDB-associated <i>SQSTM1</i> mutations.
|
31036632 |
2019 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Paget's disease of bone (PDB) is a chronic bone disorder and although genetic factors appear to play an important role in its pathogenesis, to date PDB causing mutations were identified only in the Sequestosome 1 (SQSTM1) gene at the PDB3 locus.
|
29782529 |
2018 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
A quest for clarity in bone erosion: The role of sequestosome 1 in Paget's disease of bone.
|
29907733 |
2018 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
Our results indicate that p62 predominantly suppresses murine <i>in vitro</i> osteoclast differentiation and highlight previously undetected Paget's disease-like phenotypes in p62<sup>-/-</sup> mice <i>in vivo</i>.
|
29555685 |
2018 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The mean age at diagnosis was 62 years (range 28-90); 26% of participants had a family history of PDB and 11% had Sequestosome 1 (SQSTM1) mutations.
|
28884211 |
2017 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The most frequent mutation linked to Paget's disease of bone (PDB), p.Pro392Leu within SQSTM1 gene, leads to phenotypic characteristics of PDB, but this mutation is seemingly insufficient to result in complete pagetic osteoclast phenotype, suggesting that possible environmental factors play a role in PDB pathogenesis.
|
27932202 |
2017 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
Several genes involved in the differentiation or function of osteoclast were shown to be associated with PDB or related syndrome such as SQSTM1, TNFRSF11A, TNFRSF11B, and ZNF687.
|
28389692 |
2017 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP.
|
28524179 |
2017 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Amongst the 6 family members analyzed, the p.P392L SQSTM1 mutation segregated as expected with PDB, whereas the C9orf72 expansion segregated with frontal cognitive impairment or dementia in all but one carrier.
|
26839080 |
2016 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations.
|
26772620 |
2016 |
|
Osteitis Deformans
|
0.600 |
Biomarker
|
disease |
BEFREE |
Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk.
|
26849110 |
2016 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The goal of this study is to compare the background history and phenotype of patients with PDB carrying the SQSTM1 P392L mutation to those patients without.
|
26713335 |
2016 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Heterozygous variants in SQSTM1 have been associated with Paget disease of the bone and might contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
|
27545679 |
2016 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD).
|
27163810 |
2016 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The SQSTM1/P392L germinal mutation is the most common mutation associated with PDB.
|
25241215 |
2015 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
We recruited first-degree relatives of patients with PDB [33 adult offspring (mean age 45) and 1 sibling] with a familial SQSTM1 mutation.
|
25664955 |
2015 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
A large number of mutations in SQSTM1 (which encodes sequestosome-1; also known as ubiquitin-binding protein p62) seem to account for the susceptibility to develop Paget's disease in some families; the involvement of other genes is currently under investigation.
|
26284446 |
2015 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
This mutation is the most common SQSTM1 mutation found in ALS to date, and a likely pathogenicity is supported by having an established causal role in PDB.
|
23942205 |
2014 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the SQSTM1/p62 gene have been reported in Paget's disease of bone (PDB), but they are not sufficient to induce the pagetic osteoclast (OC) phenotype.
|
25115182 |
2014 |
|
Osteitis Deformans
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Here we consider how knowledge of the impact of PDB-associated SQSTM1 mutations (several of which are now known to be relevant for ALS/FTLD) on these pathways, as well as the locations of the mutations within the p62 primary sequence, may provide new insights into ALS/FTLD disease mechanisms.
|
24486447 |
2014 |