In about 50% of these cases, these somatic mutations were the same as those found in familial IMF with the remaining cases having mutations in other sites of the gene. These other somatic mutation sites included 2 cases of p.Asp850Val (Asp=aspartate, Val=valine), 2 case of p.Asn666Lys (Asn=asparagine, Lys=lysine), and concurrent double mutations p.Arg561Cyt plus Asp666Lys in one case and p.Trp566Arg (Trp=tryptophan) plus AspN666Lys in another case. Three cases had more complex mutations involving multiple gene sites with two of them having the p.Asn666Lys mutation gene in combination with other mutations. PDGFRB gene
The PDGFRB gene product, the PDGFβ receptor, is normally highly expressed in fibroblasts and other cells of mesenchymal origin including vascular smooth muscle cells. When activated, the PDGFβ receptors tyrosine kinase stimulates cell signaling proteins such as phosphatidylinositol-3 kinase, STAT proteins, phospholipase Cγ, and GRB2 which in turn promote their parent cells to grow, proliferate, and survive for abnormally prolonged times. The PDGFβ receptor gene is a proto-oncogene, i.e. a normal gene that when mutated could form a cancer-causing oncoprotein. Studies show that the PDGFRB mutant proteins in IMF are constitutively overactive and that the tyrosine kinase inhibitor imatinib blocks the activity of the p.Arg561Cys and p.Asn666Lys mutants as well as the p.Arg561Cyt plus Asp666Lys and p.Trp566Arg plus AspN666Lys double mutants but not the p.Asp850Val mutant. Two other tyrosine kinase inhibitors, dasatinib and ponatinib, do inhibit the p.Asp850Val mutants tyrosine kinase activity. Limited initial studies suggest that these inhibitors are useful in treating severe cases of IMF.
Some available genetic tests for metachondromatosis are sequence analysis of the entire coding region, targeted variant analysis, deletion/duplication analysis, and a sequence analysis of select exons associated with the disorder. Treatment
Osteochondromas are usually painless, and in many cases, they spontaneously regress after the first or second decade of life. Most patients are asymptomatic, making medical intervention unnecessary. However, in extreme cases such as severe malalignment of the fingers and toes, surgery can be used to remove the osteochondromas. Epidemiology
Metachondromatosis is very rare, occurring in less than 1 in 1,000,000 people. Fewer than 40 cases have been reported around the world to date. References


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