Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export.
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.
Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Andrea
A
Legati
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.
Donatella
D
Giovannini
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.
Gaël
G
Nicolas
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.
Uriel
U
López-Sánchez
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.
Beatriz
B
Quintáns
Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil.
João R M
JR
Oliveira
Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Renee L
RL
Sears
Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Eliana Marisa
EM
Ramos
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Elizabeth
E
Spiteri
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.
María-Jesús
MJ
Sobrido
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.
Ángel
Á
Carracedo
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.
Cristina
C
Castro-Fernández
Neurology and Institute for Neurodegenerative Diseases, Bordeaux University Hospital and Bordeaux University, Bordeaux, France.
Stéphanie
S
Cubizolle
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Brent L
BL
Fogel
Service de Génétique Médicale, Bordeaux Hospital University Center, Bordeaux, France.
Cyril
C
Goizet
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Joanna C
JC
Jen
Division of Medicine, Buriram Hospital, Buriram, Thailand.
Suppachok
S
Kirdlarp
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.
Anthony E
AE
Lang
Medical Genetics Group, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
Zosia
Z
Miedzybrodzka
Division of Medicine, Buriram Hospital, Buriram, Thailand.
Witoon
W
Mitarnun
1] Translational Neuropharmacology, Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden. [2] Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Martin
M
Paucar
Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Henry
H
Paulson
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.
Jérémie
J
Pariente
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.
Anne-Claire
AC
Richard
Barrow Neurological Institute, Phoenix, Arizona, USA.
Naomi S
NS
Salins
Medical Genetics Group, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
Sheila A
SA
Simpson
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.
Pasquale
P
Striano
1] Translational Neuropharmacology, Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden. [2] Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Per
P
Svenningsson
Neurology and Institute for Neurodegenerative Diseases, Bordeaux University Hospital and Bordeaux University, Bordeaux, France.
François
F
Tison
Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.
Vivek K
VK
Unni
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Olivier
O
Vanakker
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
Marja W
MW
Wessels
Division of Medicine, Buriram Hospital, Buriram, Thailand.
Suppachok
S
Wetchaphanphesat
Department of Pediatrics, Children's Hospital Colorado and University of Colorado Denver, Aurora, Colorado, USA.
Michele
M
Yang
Department of Neurology, George Washington University Medical School, Washington, DC, USA.
Francois
F
Boller
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.
Dominique
D
Campion
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.
Didier
D
Hannequin
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.
Marc
0000000336162338
M
Sitbon
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.
Daniel H
DH
Geschwind
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.
Jean-Luc
JL
Battini
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.
Giovanni
0000000321051061
G
Coppola
D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D019636:Neurodegenerative Diseases / Q000235:genetics; D010375:Pedigree; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011991:Receptors, Virus / Q000235:genetics*; D000089842:Xenotropic and Polytropic Retrovirus Receptor
D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor