A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

@article{Shore2006ARM,
  title={A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva},
  author={Eileen M. Shore and Meiqi Xu and George J Feldman and David A. Fenstermacher and Tae-Joon Cho and In Choi and J. Michael Connor and Patricia L. R. Delai and David L. Glaser and Martine Lemerrer and Rolf Morhart and John G. Rogers and Roger P. Smith and James T. Triffitt and J. Andoni Urtizberea and Michael Zasloff and Matthew A. Brown and Frederick S Kaplan},
  journal={Nature Genetics},
  year={2006},
  volume={38},
  pages={525-527}
}
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G → A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of… 
Mutational analysis of the ACVR1 gene in Italian patients affected with fibrodysplasia ossificans progressiva: confirmations and advancements
TLDR
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 ACVR 1 mutation and to investigate genetic variability that may be associated with this severely debilitating disease.
Confirmation of the recurrent ACVR 1 617 G > A mutation in South Africans with fibrodysplasia ossificans progressiva
Fibrodysplasia ossificans progressiva (FOP) [OMIM 135100] is a rare genetic disorder in which ossification of connective tissue leads to severe disability. It is an autosomal dominant trait and
Classic and Atypical FOP Phenotypes are Caused by Mutations in the BMP Type I Receptor ACVR 1
Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant human disorder of bone formation that causes developmental skeletal defects and extensive debilitating bone formation within soft
A Recurrent Mutation c.617G>A in the ACVR1 Gene Causes Fibrodysplasia Ossificans Progressiva in Two Chinese Patients
TLDR
Direct sequence analysis of genomic DNA and restriction enzyme digestion demonstrated the presence of a single heterozygous c.617G>A (p.R206H) mutation in the ACVR1 gene in both patients, first reported in Chinese patients with FOP and it was de novo in both affected families.
ACVR1 Gene Mutation in Sporadic Korean Patients with Fibrodysplasia Ossificans Progressiva
TLDR
Mutation analysis confirmed a diagnosis of FOP in patients with ambiguous features, which could allow medical professionals to advise on the avoidance of provoking events to delay catastrophic flare-ups of ectopic ossifications.
Mutation Detection in Activin A Receptor, Type I (ACVR1) Gene in Fibrodysplasia Ossificans Progressiva in An Iranian Family
TLDR
A 17 year-old affected girl born to a father with chemical injury due to exposure to Mustard gas during the Iran-Iraq war, and her first degree relatives were examined to find the genetic cause of the disease.
Molecular Consequences of the ACVR1R206H Mutation of Fibrodysplasia Ossificans Progressiva*
TLDR
The impaired binding to FKBP1A and an altered subcellular distribution by R206H ACVR1 mutation may result in mild activation of osteogenic BMP-signaling in extraskeletal sites such as muscle, which eventually lead to delayed and progressive ectopic bone formation in FOP patients.
A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor.
TLDR
Findings suggest that ALK2(G356D) induces heterotopic bone formation via activation of a BMP-regulated Smad pathway, which may have caused the phenotypic differences in these patients.
A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H)
TLDR
Results give a clue to better understanding of FOP as well as of the mild clinical symptoms in the patient, and typing of SNPs located in the ∼0.5‐Mb region spanning ACVR1 and its neighbor genes suggested that 1067G > A is a de novo mutation.
Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1
TLDR
Genotype‐phenotype correlation between some ACVR1 mutations and the age of onset of heterotopic ossification or on embryonic skeletal development is observed and protein structure homology modeling predicts that each of the amino acid substitutions activates the ACVR 1 protein to enhance receptor signaling.
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TLDR
The authors have chosen to delete the Consortium name and replace it with the names of the individual consortium authors in alphabetical order in order to facilitate the electronic citation of author contributions.
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