A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date
Gregson, C. L., Hollingworth, P., Williams, M., Petrie, K. A., Bullock, A. N., Brown, M.A., Tobias, J. H., & Triffitt, J. T. (2011) A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date. Bone, 48(3), pp. 654-658.
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant condition, classically characterised by heterotopic ossification beginning in childhood and congenital great toe malformations; occurring in response to a c.617 G>A ACVR1 mutation in the functionally important glycine/serine-rich domain of exon 6. Here we describe a novel c.587 T>C mutation in the glycine/serine-rich domain of ACVR1, associated with delayed onset of heterotopic ossification and an exceptionally mild clinical course. Absence of great toe malformations, the presence of early ossification of the cervical spine facets joints, plus mild bilateral camptodactyly of the 5th fingers, together with a novel ACVR1 mutation, are consistent with the 'FOP-variant' syndrome. The c.587 T>C mutation replaces a conserved leucine with proline at residue 196. Modelling of the mutant protein reveals a steric clash with the kinase domain that will weaken interactions with FKBP12 and induce exposure of the glycine/serine-rich repeat. The mutant receptor is predicted to be hypersensitive to ligand stimulation rather than being constitutively active, consistent with the mild clinical phenotype. This case extends our understanding of the 'FOP-variant' syndrome.
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|Item Type:||Journal Article|
|Additional Information:||No file attached.|
|Keywords:||ACVR1, Fibrodysplasia ossificans progressiva, FOP, Heterotopic ossification, Mutation, activin receptor 1, analgesic agent, fk 506 binding protein, FK506 binding protein 12 kilodalton, glycine, leucine, prednisolone, proline, serine, unclassified drug, abdominal pain, ACVR1 gene, adult, amino acid substitution, article, camptodactyly, case report, cervical spine, cervical spondylosis, crystal structure, exon, female, fibrous dysplasia, flank pain, gene, gene mutation, heterozygosity, human, hydrophobicity, hydrotherapy, inflammation, masticatory muscle, onset age, phenotype, physiotherapy, protein domain, shoulder pain, tracheostomy, trismus, Activin Receptors, Type I, Base Sequence, DNA Mutational Analysis, Heterozygote, Humans, Middle Aged, Molecular Sequence Data, Myositis Ossificans, Ossification, Heterotopic, Protein Structure, Tertiary, Young Adult|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Deposited On:||01 Oct 2015 02:25|
|Last Modified:||19 Aug 2016 03:39|
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