|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
This model could be useful to elucidate molecular mechanisms leading to heterotopic ossification in FOP such as in the presence of specific ACVR1-R206H activators as Activin A.
|
28705683 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Taken together, FKBP12 binds to and suppresses mutant ALK2 proteins associated with FOP and DIPG, except for PF197-8L.
|
29551750 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
We studied 72 patients with FOP in China and analyzed their phenotypes and genotypes comprising the world's largest ethnically homogeneous population of FOP patients.
|
24051199 |
2013 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Novel asymptomatic CNS findings in patients with ACVR1/ALK2 mutations causing fibrodysplasia ossificans progressiva.
|
27565519 |
2016 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
If the diagnosis of FOP is unclear, ACVR1 mutation analysis is available at certified laboratories.
|
22131272 |
2012 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Because previous studies have shown that genetic variants of HO, such as fibrodysplasia ossificans progressiva (FOP), are caused by hyperactivating mutations of the type I bone morphogenetic protein receptor (T1-BMPR) ACVR1/ALK2, studies evaluating therapies for HO have been directed primarily toward drugs for this specific receptor.
|
28716575 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Our results therefore provide a potential therapeutic approach for the treatment of FOP disease by reducing the excessive ALK2 activity in FOP patients.
|
23861958 |
2013 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Protein modeling predicts that substitution with histidine, and only histidine, creates a pH-sensitive switch within the activation domain of the receptor that leads to ligand-independent activation of ACVR1 in fibrodysplasia ossificans progressiva.
|
17572636 |
2007 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
These results uncovered the crucial role of the Activin-A/FOP-ACVR1/ENPP2/mTOR axis in FOP pathogenesis.
|
28758906 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The dual function of ALK2 is of particular interest given the heterozygous nature of FOP, as the normal interplay between such disparate behaviors could be shifted by the presence of ALK2(R206H) receptors.
|
22174087 |
2012 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We used a new directed differentiation protocol to create human induced pluripotent stem cell (hiPSC)-derived endothelial cells (iECs) from patients with fibrodysplasia ossificans progressiva (FOP), a congenital disease of heterotopic ossification caused by an activating R206H mutation in the Activin A type I receptor (ACVR1).
|
27530160 |
2016 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We conclude that the FOP mutation ACVR1<sup>R206H</sup> is more sensitive to a number of natural ligands.
|
27713089 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
There is also a congenital and very severe form of HO that occurs in children with Fibrodysplasia Ossificans Progressiva (FOP) and is driven by activating mutations in ACVR1 encoding the type I bone morphogenetic protein (BMP) receptor ALK2.
|
28826842 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In addition, an RAR-γ agonist blocked heterotopic ossification in transgenic mice expressing activin receptor-like kinase-2 (ALK2) Q207D, a constitutively active form of the receptor that is related to ALK2 R206H found in individuals with fibrodysplasia ossificans progressiva.
|
21460849 |
2011 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In lesions from individuals with fibrodysplasia ossificans progressiva (FOP), a disease in which heterotopic ossification occurs as a result of activating ALK2 mutations, or from transgenic mice expressing constitutively active ALK2, chondrocytes and osteoblasts expressed endothelial markers.
|
21102460 |
2010 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The identification of ACVR1 as the causative gene for FOP now allows the genetic screening of FOP patients to identify the frequency of the identified recurrent ACVR1 mutation and to investigate genetic variability that may be associated with this severely debilitating disease.
|
18830232 |
2009 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations of ALK2 containing the R206 to H mutation, are present in 95% in the rare autosomal genetic disease fibrodysplasia ossificans progressiva (FOP), which leads to the development of ectopic bone formation in muscle.
|
28847510 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The clinical manifestations, the disease course, and the molecular findings of involvement of ACVR1 gene in this family are suggestive of "FOP variant" or an unusual ACVR1-related skeletal dysplasia.
|
27182040 |
2016 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
In this manuscript, we describe the molecular mechanism of the causative gene <i>ALK2</i> in FOP, mainly focusing on the prominent role of Activin A in HO.
|
31341010 |
2019 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The high fidelity phenotype-genotype relationship in these unrelated children with the most severe FOP phenotype reported to date suggests that the shared features are due to the dysregulated activity of the mutant kinase during development and postnatally, and provides vital insight into the structural biology and function of ACVR1 as well as the design of small molecule inhibitors.
|
26097044 |
2015 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Here, we studied the effects of Pasteurella multocida toxin (PMT), which activates osteoclasts and inhibits osteoblast activity, in C2C12 myoblasts expressing the mutant Alk2(R206H) receptor as model of FOP.
|
31376533 |
2019 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
While the recurrent c.617G>A; p.R206H mutation was found in all cases of classic FOP and most cases of FOP-plus, novel ACVR1 mutations occur in the FOP variants and two cases of FOP-plus.
|
19085907 |
2009 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The discovery of the FOP gene establishes a critical milestone in understanding FOP, reveals a highly conserved druggable target in the TGF-beta/bone morphogenetic protein signaling pathway and compels therapeutic approaches for the development of small molecule signal transduction inhibitors for activin-like kinase-2.
|
17477807 |
2007 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
This repression was mostly overcome by specific suppression of ALK2 expression and treatment with an ALK2 inhibitor, indicating that the inhibition of iPSC generation and maintenance observed in FOP-derived skin fibroblasts results from constitutive activation of ALK2.
|
22949078 |
2012 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In humans, activating mutations in the Type I BMP/TGFβ family member receptor, ACVR1, are associated with FOP.
|
28394244 |
2017 |