|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
The germline P392L mutation of <i>SQSTM1</i> (encoding p62) is a strong genetic risk factor for PDB in humans, and the equivalent mutation in mice (P394L) causes a PDB-like disorder.
|
30154079 |
2018 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
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
|
|
0.100 |
GeneticVariation
|
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
|
|
0.100 |
GeneticVariation
|
BEFREE |
Nine patients had the P392L mutation (21 %), 2 with familial PDB.
|
26713335 |
2016 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
These results confirmed that LNA PCR clamping is effective for the detection of SQSTM1/P392L post-zygotic mutations, which may occur in patients with PDB.
|
25241215 |
2015 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
In one p.(Pro392Leu) kindred, the carrier developed both ALS and Paget's disease of bone (PDB), and, in the p.(Glu155Lys) kindred, the father of the proband developed PDB.
|
23942205 |
2014 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Half of PDB familial forms carried a SQSTM1/p62 mutation, p62(P392L) mutation being the most frequent.
|
21962384 |
2012 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here we show that mice with a proline to leucine mutation at codon 394 of mouse sqstm1 (P394L), equivalent to the P392L SQSTM1 mutation in humans, develop a bone disorder with remarkable similarity to PDB.
|
21515589 |
2011 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L) mutation to Paget's disease.
|
21195346 |
2011 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
They also suggest that the SQSTM1 P392L mutation plays a role in PDB pathogenesis, even at early preclinical stages in healthy carriers of the P392L mutation.
|
19925894 |
2010 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Preclinical studies suggest that the p62(P392L) mutation predisposes patients to developing PD rather than causing it.
|
20392234 |
2010 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Moreover, the most-commonly reported p62 mutation, P392L, certainly contributes to the overactive state of osteoclasts in PDB.
|
19589897 |
2009 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
In addition, 194 subjects with apparently sporadic PDB were screened for the common P392L mutation by restriction enzyme digestion.
|
19257822 |
2009 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
The chance to obtain this result due to 33 independent mutation events is 3.97 x 10(-14), providing strong evidence for a founder effect of the P392L SQSTM1 mutation in Belgian, Dutch, and Spanish patients with PDB.
|
18543015 |
2008 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
The classic late-onset Paget's disease is often caused by a P392L mutation in the gene SQSTM1, which disturbs signaling pathways in osteoclasts on cell activation.
|
19032921 |
2008 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
To determine if p62 mutation is sufficient to induce PDB, we generated mice harboring a mutation causing a P-to-L (proline-to-leucine) substitution at residue 394 (the murine equivalent of human p62(P392L), the most common PDB-associated mutation).
|
18765443 |
2008 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Mutations of the SQSTM1 gene were identified in 12 of the 94 PDB patients (13%).Eight patients carried P392L.
|
17129171 |
2007 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
Mice expressing p62(P392L) developed increased osteoclast numbers and progressive bone loss, but osteoblast numbers were not coordinately increased, as is seen in Paget disease.
|
17187080 |
2007 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
The P392L mutation is the most commonly observed mutation in PDB patients and was consistently found in unrelated and familial PDB cases in the populations tested.
|
17229007 |
2006 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
We previously showed that the isolated UBA domain of p62 binds K48-linked polyubiquitin chains in vitro and that PDB-causing mutations in the UBA domain can be resolved in to those which retain (P392L and G411S) or lose (M404V and G425R) the ability to bind K48-linked polyubiquitin.
|
15765181 |
2005 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
These results provide strong evidence for a founder effect of the SQSTM1 P392L mutation in PDB patients of British descent, irrespective of family history.
|
15647816 |
2005 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
In conclusion, our study confirms that the P392L mutation is a recurrent mutation causing PDB in different populations.
|
15164150 |
2004 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
There was a relationship between serum AP activity, as a marker of the disease, and the presence or absence of the G425R and P392L mutations, the subject's age, and the presence of Paget's disease.
|
15146436 |
2004 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
We show that the Pro392 --> Leu PDB substitution mutation modifies the structure of the UBA domain by extending the N terminus of helix 1.
|
12857745 |
2003 |
|
Osteitis Deformans
|
|
0.100 |
GeneticVariation
|
BEFREE |
The P392L mutation was also found in 15 of 168 (8.9%) of patients with sporadic PDB and 0 of 160 of age- and sex-matched controls (P<0.0001).
|
12374763 |
2002 |