A recurrent PDGFRB mutation causes familial infantile myofibromatosis

Am J Hum Genet. 2013 Jun 6;92(6):996-1000. doi: 10.1016/j.ajhg.2013.04.026. Epub 2013 May 23.


Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor β (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-β promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-β as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-β in aggressive life-threatening familial forms of the disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Female
  • Genes, Dominant
  • Genetic Association Studies
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Male
  • Models, Molecular
  • Mutation, Missense*
  • Myofibromatosis / congenital*
  • Myofibromatosis / genetics
  • Pedigree
  • Protein Structure, Tertiary
  • Receptor, Notch3
  • Receptor, Platelet-Derived Growth Factor beta / chemistry
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Receptors, Notch / genetics
  • Sequence Analysis, DNA


  • NOTCH3 protein, human
  • Receptor, Notch3
  • Receptors, Notch
  • Receptor, Platelet-Derived Growth Factor beta

Supplementary concepts

  • Fibromatosis, Congenital Generalized