Abstract
Introduction: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Patients and Methods: In the present study, we present a case of FOP with marked progressive ossification of extraskeletal tissues. We investigated whether soluble factors in serum would affect the osteoblast phenotype by examining the effects of serum from this patient and control subjects on mouse osteoblastic MC3T3-E1 cells. Results: The clinical findings of this patient were compatible with FOP, and direct sequence analysis of genomic DNA demonstrated the presence of a heterozygous 617G > A (R206H) mutation of activin type 1 receptor (ACVR1). Serum from the FOP patient enhanced the level of alkaline phosphatase (ALP) in Western blotting, compared with serum from the control, in MC3T3-E1 cells. Moreover, serum from the FOP patient enhanced the levels of ALP, osteocalcin and bone morphogenetic protein-2 mRNA in these cells. Conclusion: We presented a case of FOP with progressive ossification in extra-skeletal tissues with ACVR1 mutation. The present data suggest that the serum from this patient includes some soluble factors, which might enhance the osteoblast differentiation and BMP2 expression in mouse osteoblastic cells.
Highlights
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification
Serum from the FOP patient enhanced the levels of alkaline phosphatase (ALP), osteocalcin and bone morphogenetic protein-2 mRNA in these cells
We presented a case of FOP with progressive ossification in extra-skeletal tissues with ACVR1 mutation
Summary
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Serum from the FOP patient enhanced the levels of ALP, osteocalcin and bone morphogenetic protein-2 mRNA in these cells. Conclusion: We presented a case of FOP with progressive ossification in extra-skeletal tissues with ACVR1 mutation. Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal (heterotopic) ossification, characterized by congenital malformation of the great toes. As for the pathogenesis of FOP, Shafritz et al [4] reported that the ectopic osteogenesis of FOP is associated with increased levels of bone morphogenetic protein (BMP)-4 in lymphocytes, and Olmsted et al [5] further showed that the rate of BMP-4 transcription was elevated in cells of FOP patients. Protein modeling induces destabilization of the GS domain, consistent with constitutive activation of ACVR1, expressed in many tissues, including skeletal muscle and chondrocytes.
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