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.
Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. shore@mail.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available MeSH
Activin Receptors, Type IAmino Acid SequenceAnimalsChromosomes, Human, Pair 2FemaleHumansMaleMolecular Sequence DataMutationMyositis OssificansPedigreeRNA, MessengerSequence Homology, Amino Acid
Pub Type(s)
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't