Hide and seek: Somatic SMAD3 mutations in melorheostosis

J Exp Med. 2020 May 4;217(5):e20200185. doi: 10.1084/jem.20200185.


In the current issue of JEM, Kang et al. (https://doi.org/10.1084/jem.20191499) describe somatic mutations in the SMAD3 gene causing endosteal melorheostosis. Using osteoblast models, the identified mutations are demonstrated to exert a gain-of-function mechanism, augmenting transforming growth factor (TGF) β signaling. These findings provide further insights into the genetic etiology of melorheostosis and consolidate the importance of the TGFβ pathway in skeletal disorders.

Publication types

  • Comment

MeSH terms

  • Humans
  • Melorheostosis* / genetics
  • Mutation / genetics
  • Osteoblasts / metabolism
  • Signal Transduction / genetics
  • Smad3 Protein / genetics
  • Transforming Growth Factor beta* / genetics
  • Transforming Growth Factor beta* / metabolism


  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta