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

Annika Keller*, Ana Westenberger, Maria J. Sobrido, Maria García-Murias, Aloysius Domingo, Renee L. Sears, Roberta R. Lemos, Andres Ordoñez-Ugalde, Gael Nicolas, José E.Gomes Da Cunha, Elisabeth J. Rushing, Michael Hugelshofer, Moritz C. Wurnig, Andres Kaech, Regina Reimann, Katja Lohmann, Valerija Dobričić, Angel Carracedo, Igor Petrović, Janis M. MiyasakiIrina Abakumova, Maarja Andaloussi Mäe, Elisabeth Raschperger, Mayana Zatz, Katja Zschiedrich, Jörg Klepper, Elizabeth Spiteri, Jose M. Prieto, Inmaculada Navas, Michael Preuss, Carmen Dering, Milena Janković, Martin Paucar, Per Svenningsson, Kioomars Saliminejad, Hamid R.K. Khorshid, Ivana Novaković, Adriano Aguzzi, Andreas Boss, Isabelle Le Ber, Gilles Defer, Didier Hannequin, Vladimir S. Kostić, Dominique Campion, Daniel H. Geschwind, Giovanni Coppola, Christer Betsholtz, Christine Klein, Joao R.M. Oliveira

*Corresponding author for this work
99 Citations (Scopus)


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.

Original languageEnglish
JournalNature Genetics
Issue number9
Pages (from-to)1077-1082
Number of pages6
Publication statusPublished - 01.09.2013


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