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
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Dramatic differences in susceptibility to l-DOPA-induced dyskinesia between mice that are aged before or after a nigrostriatal dopamine lesion.
TL;DR: A remarkable compensatory capacity of a damaged nigrostriatal pathway in ageing mice is revealed, and how this impacts on the response to dopaminergic therapies for Parkinson's disease is revealed.
Journal ArticleDOI
MYORG is associated with recessive primary familial brain calcification
David Arkadir,Alexander Lossos,Dolev Rahat,Muneer Abu Snineh,Ora Schueler-Furman,Silvia Nitschke,Berge A. Minassian,Berge A. Minassian,Yair Sadaka,Israela Lerer,Yuval Tabach,Vardiella Meiner +11 more
TL;DR: The genetic basis of the recessive form of primary familial brain calcification is investigated and pathways linking a novel gene with known dominant genes that cause the disease are studied.
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Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach
Javier Oliver,Javier Oliver,Rosalía Quezada Urban,Claudia Alejandra Franco Cortes,Clara Estela Díaz Velásquez,Ana Lorena Montealegre Paez,Rafael Adrián Pacheco-Orozco,Carlos Castro Rojas,Reggie García-Robles,Juan Javier López Rivera,Sandra Gaitán Chaparro,Ana Milena Gómez,Fernando Suárez Obando,Gustavo Giraldo,Maria Isabel Maya,Paula Hurtado-Villa,Ana Isabel Sánchez,Norma Serrano,Ana Isabel Orduz Galvis,Sandra Aruachan,Johanna Nuñez Castillo,Cecilia Frecha,Cecilia Riggi,Federico Jauk,Eva María Gómez García,Claudia Lorena Carranza,Vanessa Zamora,Gabriela Torres Mejia,Isabelle Romieu,Carlos Arturo Castañeda,Miluska Castillo,Rina Gitler,Adriana Antoniano,Ernesto Arturo Rojas Jiménez,Luis Enrique Romero Cruz,Fernando Vallejo Lecuona,Iván Delgado Enciso,Abril Bernardette Martinez Rizo,Alejandro Flores Carranza,Verónica Benites Godinez,Claudia Fabiola Méndez Catalá,Luis A. Herrera,Yolanda I. Chirino,Luis I. Terrazas,Sandra Perdomo,Felipe Vaca Paniagua +45 more
TL;DR: The data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC, which emphasizes the larger, unexplored genetic nature of the disease in these populations.
Journal ArticleDOI
Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects
Thierry Vilboux,May Christine V. Malicdan,Yun Min Chang,Jennifer Guo,Patricia M. Zerfas,Joshi Stephen,Andrew R. Cullinane,Joy Bryant,Roxanne Fischer,Brian P. Brooks,Wadih M. Zein,Edythe Wiggs,Christopher K. Zalewski,Andrea Poretti,Melanie M. Bryan,Meghana Vemulapalli,James C. Mullikin,Martha Kirby,Stacie M. Anderson,Nisc Comparative Sequencing Program,Marjan Huizing,Camilo Toro,William A. Gahl,Meral Gunay-Aygun +23 more
TL;DR: It is demonstrated that LAMA1 deficiency can lead to alteration in cytoskeletal dynamics, which may invariably lead to alterations in dendrite growth and axonal formation, and broadens the phenotypes associated with L AMA1 mutations.
Journal ArticleDOI
STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ.
Chaoyong He,Shayna C. Medley,Shayna C. Medley,Jang Kim,Chengyi Sun,Chengyi Sun,Hae Ryong Kwon,Hiromi Sakashita,Yair Pincu,Longbiao Yao,Danielle Eppard,Bojie Dai,William L. Berry,Timothy M. Griffin,Lorin E. Olson,Lorin E. Olson +15 more
TL;DR: Functional evidence is provided that elevated PDGFRβ signaling causes tissue wasting or overgrowth reminiscent of human genetic syndromes and that the STAT1 pathway is a crucial modulator of this phenotypic spectrum.
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
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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
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Journal ArticleDOI
Pericytes are required for blood–brain barrier integrity during embryogenesis
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