|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In humans, mutations in the Type I BMP/TGFβ family member receptor gene, ACVR1, are associated with FOP.
|
30183553 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We also have determined that constructs with FOP ACVR1 mutations that are engineered without the ligand-binding domain retain increased BMP-pSmad1/5/8 pathway activation relative to wild-type ACVR1, supporting that the mutant receptors can function through ligand-independent mechanisms either directly through mutant ACVR1 or through indirect mechanisms.
|
29097342 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
By comparison to known mutations in genetic conditions of HO such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH), DNA sequencing analysis demonstrated the presence of a commonly occurring heterozygous synonymous polymorphism (c.690G>A; E230E) in the causative gene for FOP (ACVR1/ALK2).
|
29320714 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
During the course of these studies, we also found that the activity of FOP-causing ACVR1 mutations does not by itself explain the triggered or inflammatory nature of HO in FOP, suggesting the importance of other, inflammation-introduced, factors or processes.
|
28629737 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The episodic or sporadic nature of HO associated with FOP rests with the occurrence of specific 'triggers' that push the hypersensitive ALK2-FOP receptor into full signaling mode.
|
29128351 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The structure of this complex provides a template for the design of future ALK2 inhibitors under development for the treatment of FOP and other related conditions of heterotopic ossification.
|
28918311 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Recently, activin A, a non-osteogenic member of the TGF-β family, was identified as the ligand of the mutant ALK2 in FOP, and various types of signaling inhibitors for mutant ALK2 are currently under development to establish effective treatments for FOP.
|
28754575 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We found that the Acvr1 R206H mutation caused increased BMP signaling in posttraumatic FOP lesions and early divergence from the normal skeletal muscle repair program with elevated and prolonged immune cell infiltration.
|
28986986 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation.
|
28780023 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP), is caused by mutations in the type I BMP receptor ACVR1 that lead to increased activation of the BMP-pSmad1/5/8 signaling pathway.
|
29170109 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification.
|
28985649 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP), an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification, is caused by heterozygous activating mutations in activin A receptor, type I/activin-like kinase 2 (ACVR1/ALK2).
|
29482508 |
2018 |
|
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 |
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 |
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 |
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 |
In humans, activating mutations in the Type I BMP/TGFβ family member receptor, ACVR1, are associated with FOP.
|
28394244 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The patient's genomic DNA of the coding region of ACVR1 was sequenced and analyzed for mutations known to cause FOP and novel mutations.
|
28473268 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic condition characterized by congenital malformation and progressive heterotopic ossification (HO) caused by a recurrent single nucleotide substitution at position 617 in the ACVR1 gene.
|
28390760 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
We have determined that the formation of heterotopic bone in FOP requires activation of mutant ACVR1 by Activin A, in part by showing that prophylactic inhibition of Activin A blocks HO in a mouse model of FOP.
|
28782882 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP), a disabling disorder of progressive heterotopic ossification (HEO), is caused by heterozygous gain-of- function mutations in Activin receptor A, type I (ACVR1, also known as ALK2), a bone morphogenetic protein (BMP) type I receptor.
|
28606101 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling.
|
27794120 |
2016 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints.
|
27881824 |
2016 |
|
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 |
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 |