title: Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients.
abstract: Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation.
authors.affiliation: Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford, United Kingdom.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Petrie
authors.forename: Wen Hwa
authors.initials: WH
authors.lastname: Lee
authors.forename: Alex N
authors.initials: AN
authors.lastname: Bullock
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: R Graham G
authors.initials: RG
authors.lastname: Russell
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: James T
authors.initials: JT
authors.lastname: Triffitt