2. Academic Validation
  3. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

  • Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289.
Andrea Legati 1,  Donatella Giovannini 2,  Gaël Nicolas 3,  Uriel López-Sánchez 2,  Beatriz Quintáns 4,  João R M Oliveira 5,  Renee L Sears 1,  Eliana Marisa Ramos 1,  Elizabeth Spiteri 6,  María-Jesús Sobrido 4,  Ángel Carracedo 4,  Cristina Castro-Fernández 4,  Stéphanie Cubizolle 7,  Brent L Fogel 6,  Cyril Goizet 8,  Joanna C Jen 6,  Suppachok Kirdlarp 9,  Anthony E Lang 10,  Zosia Miedzybrodzka 11,  Witoon Mitarnun 9,  Martin Paucar 12,  Henry Paulson 13,  Jérémie Pariente 14,  Anne-Claire Richard 15,  Naomi S Salins 16,  Sheila A Simpson 11,  Pasquale Striano 17,  Per Svenningsson 12,  François Tison 7,  Vivek K Unni 18,  Olivier Vanakker 19,  Marja W Wessels 20,  Suppachok Wetchaphanphesat 9,  Michele Yang 21,  Francois Boller 22,  Dominique Campion 23,  Didier Hannequin 24,  Marc Sitbon 2,  Daniel H Geschwind 25,  Jean-Luc Battini 2,  Giovanni Coppola 25
Affiliations

Affiliations

  • 1 Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • 2 1] Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Montpellier, France. [2] Université de Montpellier, Montpellier, France. [3] Laboratory of Excellence GR-Ex, Paris, France. [4] Laboratory of Excellence EpiGenMed, Montpellier, France.
  • 3 1] INSERM U1079, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Rouen, France. [2] Centre National de Référence pour les Malades Alzheimer Jeunes (CNR-MAJ), Rouen University Hospital, Rouen, France. [3] Department of Genetics, Rouen University Hospital, Rouen, France.
  • 4 1] Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Instituto de Investigación Sanitaria (IDIS, Hospital Clínico Universitario), Santiago de Compostela, Spain. [2] Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Universidad de Santiago de Compostela), Santiago de Compostela, Spain.
  • 5 Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil.
  • 6 Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • 7 Neurology and Institute for Neurodegenerative Diseases, Bordeaux University Hospital and Bordeaux University, Bordeaux, France.
  • 8 Service de Génétique Médicale, Bordeaux Hospital University Center, Bordeaux, France.
  • 9 Division of Medicine, Buriram Hospital, Buriram, Thailand.
  • 10 1] Morton and Gloria Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada. [2] Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada.
  • 11 Medical Genetics Group, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
  • 12 1] Translational Neuropharmacology, Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden. [2] Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • 13 Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
  • 14 1] INSERM, Imagerie Cérébrale et Handicaps Neurologiques, UMR 825, Pole Neurosciences, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse, France. [2] CHU de Toulouse, Université de Toulouse, Toulouse, France.
  • 15 1] INSERM U1079, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Rouen, France. [2] Centre National de Référence pour les Malades Alzheimer Jeunes (CNR-MAJ), Rouen University Hospital, Rouen, France.
  • 16 Barrow Neurological Institute, Phoenix, Arizona, USA.
  • 17 Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa 'G. Gaslini' Institute, Genoa, Italy.
  • 18 Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.
  • 19 Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
  • 20 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
  • 21 Department of Pediatrics, Children's Hospital Colorado and University of Colorado Denver, Aurora, Colorado, USA.
  • 22 Department of Neurology, George Washington University Medical School, Washington, DC, USA.
  • 23 1] INSERM U1079, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Rouen, France. [2] Centre National de Référence pour les Malades Alzheimer Jeunes (CNR-MAJ), Rouen University Hospital, Rouen, France. [3] Department of Research, Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.
  • 24 1] INSERM U1079, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Rouen, France. [2] Centre National de Référence pour les Malades Alzheimer Jeunes (CNR-MAJ), Rouen University Hospital, Rouen, France. [3] Department of Genetics, Rouen University Hospital, Rouen, France. [4] Department of Neurology, Rouen University Hospital, Rouen, France.
  • 25 1] Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. [2] Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
PMID: 25938945 DOI: 10.1038/ng.3289
Abstract

Primary familial brain calcification (PFBC) is a Neurological Disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC.

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