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. doi: 10.1038/ng1783.

Eileen M Shore ¹, Meiqi Xu, George J Feldman, David A Fenstermacher, Tae-Joon Cho, In Ho Choi, J Michael Connor, Patricia Delai, David L Glaser, Martine LeMerrer, Rolf Morhart, John G Rogers, Roger Smith, James T Triffitt, J Andoni Urtizberea, Michael Zasloff, Matthew A Brown, Frederick S Kaplan

Affiliations

Affiliation

1 Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. shore@mail.med.upenn.edu

PMID: 16642017 DOI: 10.1038/ng1783

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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