Early evidence from familial cases of osteopoikilosis and Buschke–Ollendorff syndrome demonstrated that germline LEMD3 loss‐of‐function mutations disrupt BMP/TGF‐β antagonism, occasionally in association with melorheostosis, thus providing the first link between dysregulated TGF‐β signaling and sclerosing bone dysplasias (Hellemans et al., 2004). The gene discussed is TGFB1; the disease is primary bone dysplasia with increased bone density.