Genetic Screening and Functional Characterization of PDGFRB Mutations Associated with Basal Ganglia Calcification of Unknown Etiology

Monica Sanchez-Contreras, Matthew C. Baker, Nicole A. Finch, Alexandra Nicholson, Aleksandra Wojtas, Zbigniew K. Wszolek, Owen A. Ross, Dennis W. Dickson, Rosa Rademakers

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29 Scopus citations


Three causal genes for idiopathic basal ganglia calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet-derived growth factor receptor family type β, and PDGFB, encoding PDGF-B, the specific ligand of PDGFRβ, were found implicating the PDGF-B/PDGFRβ pathway in abnormal brain calcification. In this study, we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFRβ and two previously reported mutants, p.L658P and p.R987W PDGFRβ in cell culture. We show that, in response to PDGF-BB stimulation, the p.L658P mutation completely suppresses PDGFRβ autophosphorylation, whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC.

Original languageEnglish (US)
Pages (from-to)964-971
Number of pages8
JournalHuman mutation
Issue number8
StatePublished - Aug 2014



  • BGC
  • Basal ganglia calcification
  • Fahr disease
  • IBGC

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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