Specific classes of de novo heterozygous gain-of-function pathogenic variants of the PDGFRB (platelet-derived growth factor receptor-beta) cause a distinctive overgrowth syndrome, named the Kosaki overgrowth syndrome (KOGS) (OMIM #616592).
Here, we report the identification of a mutation in PDGFRB, c.1696T>C p.(Trp566Arg), in two unrelated patients with skeletal overgrowth, further confirming the existence of PDGFRB-related overgrowth syndrome arising from mutations in the juxtamembrane domain of PDGFRB.
In conclusion, the PDGFRB mutations previously identified in familial IM and overgrowth syndrome activate the receptor in the absence of ligand, supporting the hypothesis that these mutations cause the diseases.