Abstract
Fibrodysplasia ossificans progressiva (FOP), characterized by congenital malformation of bones, is an autosomal dominant disorder. This is a rare genetic disorder and its worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. It is regarded as one of the intractable disorders, which is not only an extremely disabling disease but also a condition of considerably shortened lifespan. Although the genetic defects of FOP are not completely known, several clinical and animal model studies have implicated that mutations in bone morphogenetic proteins, their receptors, and activin receptor type IA (ACVR1) genes are associated with FOP primarily. The noggin (NOG) gene has also been reported in some studies. In most of the cases of FOP, the mutation was found as 'de novo' however there is paternal age effect on mutations. Unfortunately, at present there is no efficient treatment for FOP. The recent discoveries of genetic basis of FOP provide a clue to the underlying pathophysiology and potential therapy. This review article focuses on the genetic mutations in FOP, their usage as diagnostic markers, and possible target specific drug development to treat FOP patients.
Highlights
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of dysregulated cellular differentiation, which is characterized by congenital malformation of the great toes during embryonic skeletal development and by progressive heterotopic endochondral ossification of the connective tissue post-natally that forms qualitatively normal bone in characteristic extraskeletal sites (Ratbi et al, 2010; Pignolo et al, 2011; Chakkalakal et al, 2012)
FOP is a rare genetic disorder, in which, mutations in some genes related to bone morphogenesis have been reported
Kan et al (2004) developed a unique transgenic mouse line that overexpresses BMP4 under the control of the neuronspecific enolase (NSE) promoter, which develops a FOPlike phenotype. Mating of these animals with transgenic animals that overexpress the bone morphogenetic proteins (BMPs) inhibitor NOG, prevents the disorder, and confirmed the role of BMP4 in the pathogenesis of the disease. This remarkable animal model provided a good opportunity to further study the role of the BMP signaling pathway in heterotopic ossification and to improve the understanding of the clinical aspects of FOP (Kan et al, 2004)
Summary
Fibrodysplasia ossificans progressiva (FOP), characterized by congenital malformation of bones, is an autosomal dominant disorder. This is a rare genetic disorder and its worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. It is regarded as one of the intractable disorders, which is an extremely disabling disease and a condition of considerably shortened lifespan. The genetic defects of FOP are not completely known, several clinical and animal model studies have implicated that mutations in bone morphogenetic proteins, their receptors, and activin receptor type IA (ACVR1) genes are associated with FOP primarily.
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