A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva - PubMed (original) (raw)

doi: 10.1038/ng1783. Epub 2006 Apr 23.

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

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A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Eileen M Shore et al. Nat Genet. 2006 May.

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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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