Fibrodysplasia ossificans progressiva: a blueprint for metamorphosis
| Autor: | Eileen M. Shore, Robert J. Pignolo, Haitao Wang, Frederick S. Kaplan, Vitali Y. Lounev |
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| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Mutation business.industry General Neuroscience Myositis ossificans ACVR1 Bioinformatics Bone morphogenetic protein medicine.disease medicine.disease_cause General Biochemistry Genetics and Molecular Biology History and Philosophy of Science Fibrodysplasia ossificans progressiva medicine Missense mutation Heterotopic ossification business Endochondral ossification |
| Zdroj: | Annals of the New York Academy of Sciences. 1237:5-10 |
| ISSN: | 0077-8923 |
| Popis: | The most important milestone in understanding a genetic disease is the identification of the causative mutation. However, such knowledge is often insufficient to decipher the pathophysiology of the disorder or to effectively treat those affected. Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling, genetic disease of progressive heterotopic endochondral ossification (HEO) enabled by missense mutations that promiscuously and provisionally activate ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, in all affected individuals. While activating mutations of the ACVR1/ALK2 receptor are necessary, disease activity and progression also depend on altered cell and tissue physiology. Recent findings identify inflammatory and immunological factors, vascular-derived mesenchymal stem cells, and a hypoxic lesional microenvironment that trigger, promote, and enable episodic progression of FOP in the setting of the genetic mutation. Effective therapies for FOP will need to consider these seminal pathophysiologic interactions. |
| Databáze: | OpenAIRE |
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