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

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.

Classic and Atypical FOP Phenotypes are Caused by Mutations in the BMP Type I Receptor ACVR 1

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.

Confirmation of the recurrent ACVR 1 617 G > A mutation in South Africans with fibrodysplasia ossificans progressiva

It is investigated whether the commonly reported ACVR1/ ALK2 617G>A recurrent mutation also causes FOP in indigenous South Africans, and the main features of Fop in the affected South Africans were consistent with the literature.

A Recurrent Mutation c.617G>A in the ACVR1 Gene Causes Fibrodysplasia Ossificans Progressiva in Two Chinese Patients

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

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

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*

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.

A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H)

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

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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References

SHOWING 1-10 OF 34 REFERENCES

Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP)

It is concluded that mutations in the coding region of noggin are not associated with FOP, and elevated levels of bone morphogenetic protein 4 occur in lymphoblastoid cells and in lesional cells of patients with Fop.

Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31.

The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0), and crossover events localize the putative FOP gene within a 36-cM interval which contains at least one gene involved in the bone morphogenetic protein-signaling pathway.

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

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.

Paresis of a Bone Morphogenetic Protein-Antagonist Response in a Genetic Disorder of Heterotopic Skeletogenesis

The findings suggest the potential usefulness of BMP-antagonist-based strategies in the therapy for patients with fibrodysplasia ossificans progressiva and other disorders of excessive bone formation and suggest the importance of modulating endogenous BMP -antagonist activity in therapeutic applications of B MP-induced osteogenesis.

Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva.

Overexpression of a potent bone-inducing morphogen (bone morphogenetic protein 4) in lymphocytes is associated with the disabling ectopic osteogenesis of fibrodysplasia ossificans progressiva.

Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome

It is reported that 22 of 129 individuals with Noonan syndrome without PTPN11 or KRAS mutation have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor, and this finding defines a new mechanism by which upregulation of the RAS pathway can profoundly change human development.

The genetics of fibrodysplasia ossificans progressiva

The recent identification of several small, additional families with inheritance of classic features of FOP has provided the opportunity to expand positional cloning efforts to identify the mutated gene in FOP through whole-genome linkage analyses.

Fibrodysplasia Ossificans Progressiva (FOP), a Disorder of Ectopic Osteogenesis, Misregulates Cell Surface Expression and Trafficking of BMPRIA

FOP lymphocytes, a model system for exploring the BMP pathway in patients, exhibit a defect in BMPRIA internalization and increased activation of downstream signaling, suggesting that altered BMP receptor trafficking underlies ectopic bone formation in this disease.

Corrigendum: Lamin B1 duplications cause autosomal dominant leukodystrophy

The construct described as moody-GAL4 has a name that was assigned to a different construct in a previously published paper, so it should be referred to as SPG- GAL4 (for 'sub-perineural-glia-gAL4').