TUESDAY, April 25 (HealthDay News) -- Scientists have discovered the genetic mutation that causes fibrodysplasia ossificans progressiva (FOP), a rare and severely disabling autosomal dominant disorder characterized by episodic and progressive bone formation, according to a study published online April 23 in Nature Genetics.
Frederick Kaplan, M.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues studied seven families affected by FOP as well as 32 sporadic cases.
In all of the affected patients, the researchers mapped FOP to chromosome 2q23-24 by linkage analysis and identified a heterozygous mutation (617G-A; R206H) in the activation domain of ACVR1, a bone morphogenetic protein (BMP) type I receptor. ACVR1, which is expressed in muscle and chondrocytes, upregulates BMP4, downregulates BMP antagonists, and can stimulate joint fusion, making it a strong candidate gene for FOP, the report indicates.
"Identification of a specific disease-causing mutation in ACVR1 has critical diagnostic and therapeutic implications for FOP and identifies a new investigative focus for skeletal biology and regenerative medicine," the authors conclude.