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.

Statistics. We used JMP software from SAS (versions 13 or 14) for all analyses. Data are presented with all data points plotted. Overlayed diamonds represent mean, 95% CI, and overlap marks (horizontal lines above and below the mean line), which define statistical significant difference between groups if not overlapping (P < 0.05). Groups were compared with 1-way ANOVA, applying a Tukey-Kramer posttest correcting for multiple comparisons. A P value of less than 0.05 was considered statistically significant.Study approval. All animal studies were approved by the cantonal veterinary authorities "Kantonale Tierversuchskommission Zürich." The clinical study (CSF sampling) was approved by the local ethical review board of the Kanton of Zurich, and written consent was obtained from all patients or their legal representatives.

Higher IL-6 levels are associated with worse clinical outcome and the occurrence of DINDs. Because IL-6 levels were significantly elevated in the early phase, they might be a useful parameter to monitor.