title: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva.
abstract: 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 ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.
authors.affiliation: Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. shore@mail.med.upenn.edu
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
authors.forename: Meiqi
authors.initials: M
authors.lastname: Xu
authors.forename: George J
authors.initials: GJ
authors.lastname: Feldman
authors.forename: David A
authors.initials: DA
authors.lastname: Fenstermacher
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.forename: In Ho
authors.initials: IH
authors.lastname: Choi
authors.forename: J Michael
authors.initials: JM
authors.lastname: Connor
authors.forename: Patricia
authors.initials: P
authors.lastname: Delai
authors.forename: David L
authors.initials: DL
authors.lastname: Glaser
authors.forename: Martine
authors.initials: M
authors.lastname: LeMerrer
authors.forename: Rolf
authors.initials: R
authors.lastname: Morhart
authors.forename: John G
authors.initials: JG
authors.lastname: Rogers
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: James T
authors.initials: JT
authors.lastname: Triffitt
authors.forename: J Andoni
authors.initials: JA
authors.lastname: Urtizberea
authors.forename: Michael
authors.initials: M
authors.lastname: Zasloff
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
mesh_terms: D030201:Activin Receptors, Type I / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002889:Chromosomes, Human, Pair 2; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009221:Myositis Ossificans / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D012333:RNA, Messenger; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I