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

Andrea Legati, Donatella Giovannini, Gaël Nicolas, Uriel López-Sánchez, Beatriz Quintáns, João R M Oliveira, Renee L Sears, Eliana Marisa Ramos, Elizabeth Spiteri, María-Jesús Sobrido, Ángel Carracedo, Cristina Castro-Fernández, Stéphanie Cubizolle, Brent L Fogel, Cyril Goizet, Joanna C Jen, Suppachok Kirdlarp, Anthony E Lang, Zosia Miedzybrodzka, Witoon MitarnunMartin Paucar, Henry Paulson, Jérémie Pariente, Anne-Claire Richard, Naomi S Salins, Sheila A Simpson, Pasquale Striano, Per Svenningsson, François Tison, Vivek K Unni, Olivier Vanakker, Marja W Wessels, Suppachok Wetchaphanphesat, Michele Yang, Francois Boller, Dominique Campion, Didier Hannequin, Marc Sitbon, Daniel H Geschwind, Jean-Luc Battini, Giovanni Coppola

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206 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)579-581
Number of pages3
JournalNature Genetics
Issue number6
Early online date4 May 2015
Publication statusPublished - Jun 2015

Bibliographical note

Date of Acceptance: 06/05/2015

We acknowledge and thank all of the participants and families for their valuable contributions to our study; our clinical staff and laboratory members, J. DeYoung and the University of California Los Angeles (UCLA) Neuroscience Genomics Core, J. Touhami and J. Laval for their assistance and constant support; and the National Heart, Lung, and Blood Institute (NHLBI) GO Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the Women's Health Initiative (WHI) Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). We are also indebted to the Montpellier Rio Imaging (MRI) platform for flow cytometry experiments. This work was funded by the US National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01NS040752 to D.H.G.), by Association Française contre les Myopathies (AFM) and Ligue Nationale contre le Cancer (Comité de l'Hérault; to J.-L.B.), and by Fondation pour la Recherche Médicale (FRM) and a FEDER European Union Languedoc-Roussillon grant (Transportome; to M.S.). We also acknowledge the support of the National Institute of Neurological Disorders and Stroke Informatics Center for Neurogenetics and Neurogenomics (PSNS062691). D.G. was supported by FRM, Institut National du Cancer (INCa) and Labex GR-Ex (ANR-11-LABX-0051) fellowships, and U.L.-S. was supported by a Labex EpiGenMed (ANR-10-LABX-12-01) fellowship; Labex is funded by the program 'Investissements d'Avenir' of the French National Research Agency. J.-L.B. and M.S. were supported by INSERM. M.-J.S. and B.Q. are supported by the Fondo de Investigación Sanitaria, grant PI12/00742; INNOPHARMA project MINECO-USC; and FEDER funds. M.-J.S. and B.Q. hold research contracts from the Institute of Health Carlos III–SERGAS. J.R.M.O. acknowledges funding from FACEPE (APQ 1831-4.01/12) and CNPq (457556/2013-7; 480255/2013-0; 307909/2012-3). B.L.F. is funded by US National Institutes of Health grants K08MH086297 (National Institute of Mental Health) and R01NS082094 (National Institute of Neurological Disorders and Stroke). G.N., A.-C.R., D.H. and D.C. are supported by INSERM, the University Hospital of Rouen and the French CNR-MAJ.


  • medical genetics
  • neurodegenerative diseases


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