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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)579-581
Number of pages3
JournalNature Genetics
Volume47
Issue number6
Early online date4 May 2015
DOIs
Publication statusPublished - Jun 2015

Fingerprint

Phosphates
Mutation
Brain
Proto-Oncogene Proteins c-sis
Platelet-Derived Growth Factor beta Receptor
Basal Ganglia
Homeostasis
Genes

Keywords

  • medical genetics
  • neurodegenerative diseases

Cite this

Legati, A., Giovannini, D., Nicolas, G., López-Sánchez, U., Quintáns, B., Oliveira, J. R. M., ... Coppola, G. (2015). Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nature Genetics, 47(6), 579-581. https://doi.org/10.1038/ng.3289

Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. / Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João R M; Sears, Renee L; Ramos, Eliana Marisa; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L; Goizet, Cyril; Jen, Joanna C; Kirdlarp, Suppachok; Lang, Anthony E; Miedzybrodzka, Zosia; Mitarnun, Witoon; Paucar, Martin; Paulson, Henry; Pariente, Jérémie; Richard, Anne-Claire; Salins, Naomi S; Simpson, Sheila A; Striano, Pasquale; Svenningsson, Per; Tison, François; Unni, Vivek K; Vanakker, Olivier; Wessels, Marja W; Wetchaphanphesat, Suppachok; Yang, Michele; Boller, Francois; Campion, Dominique; Hannequin, Didier; Sitbon, Marc; Geschwind, Daniel H; Battini, Jean-Luc; Coppola, Giovanni.

In: Nature Genetics, Vol. 47, No. 6, 06.2015, p. 579-581.

Research output: Contribution to journalArticle

Legati, A, Giovannini, D, Nicolas, G, López-Sánchez, U, Quintáns, B, Oliveira, JRM, Sears, RL, Ramos, EM, Spiteri, E, Sobrido, M-J, Carracedo, Á, Castro-Fernández, C, Cubizolle, S, Fogel, BL, Goizet, C, Jen, JC, Kirdlarp, S, Lang, AE, Miedzybrodzka, Z, Mitarnun, W, Paucar, M, Paulson, H, Pariente, J, Richard, A-C, Salins, NS, Simpson, SA, Striano, P, Svenningsson, P, Tison, F, Unni, VK, Vanakker, O, Wessels, MW, Wetchaphanphesat, S, Yang, M, Boller, F, Campion, D, Hannequin, D, Sitbon, M, Geschwind, DH, Battini, J-L & Coppola, G 2015, 'Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export', Nature Genetics, vol. 47, no. 6, pp. 579-581. https://doi.org/10.1038/ng.3289
Legati A, Giovannini D, Nicolas G, López-Sánchez U, Quintáns B, Oliveira JRM et al. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nature Genetics. 2015 Jun;47(6):579-581. https://doi.org/10.1038/ng.3289
Legati, Andrea ; Giovannini, Donatella ; Nicolas, Gaël ; López-Sánchez, Uriel ; Quintáns, Beatriz ; Oliveira, João R M ; Sears, Renee L ; Ramos, Eliana Marisa ; Spiteri, Elizabeth ; Sobrido, María-Jesús ; Carracedo, Ángel ; Castro-Fernández, Cristina ; Cubizolle, Stéphanie ; Fogel, Brent L ; Goizet, Cyril ; Jen, Joanna C ; Kirdlarp, Suppachok ; Lang, Anthony E ; Miedzybrodzka, Zosia ; Mitarnun, Witoon ; Paucar, Martin ; Paulson, Henry ; Pariente, Jérémie ; Richard, Anne-Claire ; Salins, Naomi S ; Simpson, Sheila A ; Striano, Pasquale ; Svenningsson, Per ; Tison, François ; Unni, Vivek K ; Vanakker, Olivier ; Wessels, Marja W ; Wetchaphanphesat, Suppachok ; Yang, Michele ; Boller, Francois ; Campion, Dominique ; Hannequin, Didier ; Sitbon, Marc ; Geschwind, Daniel H ; Battini, Jean-Luc ; Coppola, Giovanni. / Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. In: Nature Genetics. 2015 ; Vol. 47, No. 6. pp. 579-581.
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note = "Date of Acceptance: 06/05/2015 Acknowledgments 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 Fran{\cc}aise contre les Myopathies (AFM) and Ligue Nationale contre le Cancer (Comit{\'e} de l'H{\'e}rault; to J.-L.B.), and by Fondation pour la Recherche M{\'e}dicale (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 Investigaci{\'o}n 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.",
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TY - JOUR

T1 - Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

AU - Legati, Andrea

AU - Giovannini, Donatella

AU - Nicolas, Gaël

AU - López-Sánchez, Uriel

AU - Quintáns, Beatriz

AU - Oliveira, João R M

AU - Sears, Renee L

AU - Ramos, Eliana Marisa

AU - Spiteri, Elizabeth

AU - Sobrido, María-Jesús

AU - Carracedo, Ángel

AU - Castro-Fernández, Cristina

AU - Cubizolle, Stéphanie

AU - Fogel, Brent L

AU - Goizet, Cyril

AU - Jen, Joanna C

AU - Kirdlarp, Suppachok

AU - Lang, Anthony E

AU - Miedzybrodzka, Zosia

AU - Mitarnun, Witoon

AU - Paucar, Martin

AU - Paulson, Henry

AU - Pariente, Jérémie

AU - Richard, Anne-Claire

AU - Salins, Naomi S

AU - Simpson, Sheila A

AU - Striano, Pasquale

AU - Svenningsson, Per

AU - Tison, François

AU - Unni, Vivek K

AU - Vanakker, Olivier

AU - Wessels, Marja W

AU - Wetchaphanphesat, Suppachok

AU - Yang, Michele

AU - Boller, Francois

AU - Campion, Dominique

AU - Hannequin, Didier

AU - Sitbon, Marc

AU - Geschwind, Daniel H

AU - Battini, Jean-Luc

AU - Coppola, Giovanni

N1 - Date of Acceptance: 06/05/2015 Acknowledgments 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.

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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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KW - neurodegenerative diseases

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DO - 10.1038/ng.3289

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