Journal ArticleDOI
Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice
Annika Keller,Annika Keller,Annika Keller,Ana Westenberger,María Jesús Sobrido,María García-Murias,Aloysius Domingo,Renee L. Sears,R. R. Lemos,Andrés Ordóñez-Ugalde,Gaël Nicolas,José Eriton Gomes da Cunha,Elisabeth J. Rushing,Michael Hugelshofer,Moritz C. Wurnig,Andres Kaech,Regina Reimann,Katja Lohmann,Valerija Dobricic,Angel Carracedo,Igor Petrović,Janis M. Miyasaki,Irina Abakumova,Maarja Mäe,Maarja Mäe,Elisabeth Raschperger,Elisabeth Raschperger,Mayana Zatz,Katja Zschiedrich,Jörg Klepper,Elizabeth Spiteri,Elizabeth Spiteri,J.M. Prieto,I. Navas,Michael Preuss,Carmen Dering,Milena Jankovic,Martin Paucar,Per Svenningsson,Kioomars Saliminejad,Hamid Reza Khorram Khorshid,Ivana Novakovic,Adriano Aguzzi,Andreas Boss,Isabelle Le Ber,Gilles Defer,Didier Hannequin,Vladimir S. Kostic,Dominique Campion,Daniel H. Geschwind,Giovanni Coppola,Christer Betsholtz,Christer Betsholtz,Christine Klein,João Ricardo Mendes de Oliveira +54 more
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TLDR
The data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.Abstract:
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.read more
Citations
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Journal ArticleDOI
Astrocyte-microglial association and matrix composition are common events in the natural history of primary familial brain calcification.
Khayrun Nahar,Thibaud Lebouvier,Thibaud Lebouvier,Maarja Andaloussi Mäe,Anne Konzer,Jonas Bergquist,Yvette Zarb,Bengt Johansson,Christer Betsholtz,Christer Betsholtz,Michael Vanlandewijck,Michael Vanlandewijck +11 more
TL;DR: Gen expression and spatial correlations suggest that astrocytes are intimately linked to the calcification process in PFBC, and lack of pericytes and increase in permeability of the blood–brain barrier are likely not the causal triggers for PFBC pathogenesis.
Journal ArticleDOI
Primary familial brain calcification in the 'IBGC2' kindred: All linkage roads lead to SLC20A2.
Karen Grütz,Claudia B. Volpato,Aloysius Domingo,Daniel Alvarez-Fischer,Uwe Gebert,Günther Schifferle,Ebba Buffone,Zbigniew K. Wszolek,Rosa Rademakers,Andreas Ferbert,Andrew A. Hicks,Christine Klein,Peter P. Pramstaller,Ana Westenberger +13 more
TL;DR: The genetic cause of primary familial brain calcification in the ‘IBGC2’ kindred is elucidated.
Journal ArticleDOI
Parkinsonism and inborn errors of metabolism.
TL;DR: IEMs causing this neurological syndrome are reviewed and diagnostic approaches depending on the age of onset and the associated clinical and neuroimaging features are proposed.
Journal ArticleDOI
White matter involvement in a family with a novel PDGFB mutation.
Roberta Biancheri,Mariasavina Severino,Angela Robbiano,Michele Iacomino,Massimo Del Sette,Carlo Minetti,Mariarosaria Cervasio,Marialaura Del Basso De Caro,Pasquale Striano,Federico Zara +9 more
TL;DR: Primary familial brain calcification (PFBC) (formerly idiopathic basal ganglia calcification; Fahr disease) is an autosomal dominant cerebral microvascular calcifying disorder with variable clinical and imaging features.
Journal ArticleDOI
Underestimated disease prevalence and severe phenotypes in patients with biallelic variants: A cohort study of primary familial brain calcification from China.
Si Chen,Zhidong Cen,Feng Fu,You Chen,Xinhui Chen,Dehao Yang,Haotian Wang,Hongwei Wu,Xiaosheng Zheng,Fei Xie,Zhiyuan Ouyang,Weiguo Tang,Shuhong Zhang,Lili Yin,Yunqian Zhang,Peiying Meng,Xuzhen Zhu,Hongwei Zhang,Feifei Jiang,Kaiyu Zhang,Juping He,Danhong Zhang,Hanqiao Ming,Daqiao Song,Zhiping Zhou,Yong Luo,Qun Gu,Yongkun Su,Xinxiao Wu,Haiyan Tang,Chenglong Wu,Weiqing Chen,Jing-Yu Liu,Wei Luo,Xuerong Huang,Shaowei Fu,Wenhai Chen,Yanbin Huang,Likang Lan,Xiaofen Zhu,Zhijun Xu,Huayun Huang,Lifeng Zhou,Zilong Chen,Minfang Lou,Binglan Wang,Yi Tan,Manlian Zhu,Weijun Hong,Feng Wang,Gonghua Pan,Aimin Shao,Weiying Li,Haijun Li,Na Zhao,Haoyu Hu,Yaxi Zhang,Mengjia Lian,Jieying Li,Xueli Cai,Zixian Luo,Yan Zhou,Xiaoyi Lu,Li Ma,Enkui Xia,Xiaoluo Zhang +65 more
TL;DR: A higher proportion of genetically confirmed PFBC probands who were asymptomatic would be overlooked due to clinical selection bias, leading to underestimation of the disease prevalence, which should be focused on in genetic counseling.
References
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Journal ArticleDOI
Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor
TL;DR: Structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role ofPDGF in normal and diseased tissues are discussed.
Journal ArticleDOI
Pericytes regulate the blood–brain barrier
Annika Armulik,Guillem Genové,Maarja Mäe,Maya H. Nisancioglu,Elisabet Wallgard,Elisabet Wallgard,Colin Niaudet,Liqun He,Liqun He,Jenny Norlin,Per Lindblom,Karin Strittmatter,Karin Strittmatter,Bengt Johansson,Christer Betsholtz +14 more
TL;DR: A novel and critical role for pericytes is indicated in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the blood–brain barrier.
Journal ArticleDOI
Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice
TL;DR: Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts, and endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells.
Journal ArticleDOI
Role of platelet-derived growth factors in physiology and medicine.
TL;DR: Basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts are reviewed.
Journal ArticleDOI
Pericytes are required for blood–brain barrier integrity during embryogenesis
TL;DR: Pericytes regulate functional aspects of the blood–brain barrier, including the formation of tight junctions and vesicle trafficking in CNS endothelial cells, but inhibit the expression of molecules that increase vascular permeability and CNS immune cell infiltration.
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