Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice

Nat Genet. 2013 Sep;45(9):1077-82. doi: 10.1038/ng.2723. Epub 2013 Aug 4.


Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait (idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor β (PDGF-Rβ) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-Rβ. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Basal Ganglia Diseases / diagnosis
  • Basal Ganglia Diseases / genetics*
  • Basal Ganglia Diseases / pathology*
  • Brain / metabolism
  • Brain / pathology
  • Calcinosis / genetics*
  • Disease Models, Animal
  • Female
  • Gene Order
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Knockout
  • Mutation*
  • Pedigree
  • Proto-Oncogene Proteins c-sis / genetics*
  • Tomography, X-Ray Computed


  • Proto-Oncogene Proteins c-sis

Associated data

  • RefSeq/NC_000022
  • RefSeq/NM_002608
  • RefSeq/NP_002599