A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva.
Nat Genet. 2006 May; 38(5):525-7.NGen

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.

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Authors+Show Affiliations

Shore EM
Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. shore@mail.med.upenn.edu
Xu M
No affiliation info available
Feldman GJ
No affiliation info available
Fenstermacher DA
No affiliation info available
Cho TJ
No affiliation info available
Choi IH
No affiliation info available
Connor JM
No affiliation info available
Delai P
No affiliation info available
Glaser DL
No affiliation info available
LeMerrer M
No affiliation info available
Morhart R
No affiliation info available
Rogers JG
No affiliation info available
Smith R
No affiliation info available
Triffitt JT
No affiliation info available
Urtizberea JA
No affiliation info available
Zasloff M
No affiliation info available
Brown MA
No affiliation info available
Kaplan FS
No 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

Language

eng

PubMed ID

16642017