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

Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Facucho-Oliveira, Joao; 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 Arce, 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 M.; Wessels, Marja W; Wetchaphanphesat, Suppachok; Yang, Michele L; Boller, François; Campion, Dominique; Hannequin, Didier; Sitbon, Marc; Geschwind, Daniel H.; Battini, Jean-Luc; Coppola, Giovanni

doi:10.1038/ng.3289

ScienceOpen: research and publishing network

For Publishers

For Researchers

Blog
About

Search
Advanced search

views

recommends

Record: found
Abstract: found
Article: not found

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

research-article

Author(s): Andrea Legati ¹ , Donatella Giovannini ² ^, ³ ^, ⁴ , Gaël Nicolas ⁵ ^, ⁶ , Uriel López-Sánchez ² ^, ³ ^, ⁴ , Beatriz Quintáns ⁷ , João Oliveira ⁸ , Renee L. Sears ¹ , Eliana Marisa Ramos ¹ , Elizabeth Spiteri ⁹ , María-Jesús Sobrido ⁷ , Ángel Carracedo ⁷ , Cristina Castro-Fernández ⁷ , Stéphanie Cubizolle ¹⁰ , Brent L. Fogel ⁹ , Cyril Goizet ¹¹ , Joanna C. Jen ⁹ , Suppachok Kirdlarp ¹² , Anthony E. Lang ¹³ , Zosia Miedzybrodzka ¹⁴ , Witoon Mitarnun ¹² , Martin Paucar ¹⁵ , Henry Paulson ¹⁶ , Jérémie Pariente ¹⁷ , Anne-Claire Richard ⁵ , Naomi S. Salins ¹⁸ , Sheila A. Simpson ¹⁴ , Pasquale Striano ¹⁹ , Per Svenningsson ¹⁵ , François Tison ¹⁰ , Vivek K. Unni ²⁰ , Olivier Vanakker ²¹ , Marja W. Wessels ²² , Suppachok Wetchaphanphesat ¹² , Michele Yang ²³ , Francois Boller ²⁴ , Dominique Campion ⁵ ^, ²⁵ , Didier Hannequin ⁵ ^, ⁶ ^, ²⁶ , Marc Sitbon ² ^, ³ ^, ⁴ , Daniel H. Geschwind ¹ ^, ⁹ , Jean-Luc Battini ² ^, ³ ^, ⁴ , Giovanni Coppola ¹ ^, ⁹

Publication date (Electronic): 04 May 2015

Journal: Nature genetics

Read this article at

ScienceOpenPublisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions, thus far associated with SLC20A2, PDGFB, or PDGFRB mutations. We identified in multiple PFBC families mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, providing a direct evidence of an impact of XPR1 and phosphate homeostasis in PFBC.

Related collections

Most cited references 23

Record: found
Abstract: found
Article: not found

The emerging importance of the SPX domain-containing proteins in phosphate homeostasis.

A Bulak Arpat, Chuang Wang, David Secco … (2012)

Plant growth and development are strongly influenced by the availability of nutrients in the soil solution. Among them, phosphorus (P) is one of the most essential and most limiting macro-elements for plants. In the environment, plants are often confronted with P starvation as a result of extremely low concentrations of soluble inorganic phosphate (Pi) in the soil. To cope with these conditions, plants have developed a wide spectrum of mechanisms aimed at increasing P use efficiency. At the molecular level, recent studies have shown that several proteins carrying the SPX domain are essential for maintaining Pi homeostasis in plants. The SPX domain is found in numerous eukaryotic proteins, including several proteins from the yeast PHO regulon, involved in maintaining Pi homeostasis. In plants, proteins harboring the SPX domain are classified into four families based on the presence of additional domains in their structure, namely the SPX, SPX-EXS, SPX-MFS and SPX-RING families. In this review, we highlight the recent findings regarding the key roles of the proteins containing the SPX domain in phosphate signaling, as well as providing further research directions in order to improve our knowledge on P nutrition in plants, thus enabling the generation of plants with better P use efficiency. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

0 comments Cited 105 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice.

C Wurnig, Isabelle Le Ber, Ivana Novaković … (2013)

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.

0 comments Cited 101 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification.

L. Maréchal-Drouard, Olivier Martinaud, X Ayrignac … (2013)

To identify a new idiopathic basal ganglia calcification (IBGC)-causing gene. In a 3-generation family with no SLC20A2 mutation, we performed whole exome sequencing in 2 affected first cousins, once removed. Nonsynonymous coding variants, splice acceptor and donor site variants, and frameshift coding indels (NS/SS/I) were filtered against dbSNP131, the HapMap Project, 1000 Genomes Project, and our in-house database including 72 exomes. Seventeen genes were affected by identical unknown NS/SS/I variations in the 2 patients. After screening the relatives, the p.Leu658Pro substitution within the PDGFRB gene remained the sole unknown mutation segregating with the disease in the family. This variation, which is predicted to be highly damaging, was present in 13 of 13 affected subjects and absent in 8 relatives without calcifications. Sequencing PDGFRB of 19 other unrelated IBGC cases allowed us to detect another potentially pathogenic substitution within PDGFRB, p.Arg987Trp, also predicted to be highly damaging. PDGFRB encodes a protein involved in angiogenesis and in the regulation of inorganic phosphate (Pi) transport in vascular smooth muscle cells via Pit-1, a Pi transporter encoded by SLC20A1. Mutations of PDGFRB further support the involvement of this biological pathway in IBGC pathophysiology.

0 comments Cited 81 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 9216904

Journal ID (pubmed-jr-id): 2419

Journal ID (nlm-ta): Nat Genet

Journal ID (iso-abbrev): Nat. Genet.

Title: Nature genetics

ISSN (Print): 1061-4036

ISSN (Electronic): 1546-1718

Publication date Nihms-submitted: 26 June 2015

Publication date (Electronic): 04 May 2015

Publication date (Print): June 2015

Publication date PMC-release: 01 December 2015

Volume: 47

Issue: 6

Pages: 579-581

Affiliations

[1 ]Department of Psychiatry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

[2 ]Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France

[3 ]Université de Montpellier, F-34293 Cedex 5, Montpellier, France

[4 ]Laboratories of Excellence GR-Ex, Paris and EpiGenMed, Montpellier, France

[5 ]Inserm U1079, IRIB, University of Rouen and CNR-MAJ, Rouen University Hospital, Rouen, France

[6 ]Department of Genetics, Rouen University Hospital, Rouen, France

[7 ]Fundación Pública Galega de Medicina Xenómica-SERGAS-IDIS (Hospital Clínico Universitario) and Grupo de Medicina Xenómica-CIBERER (Universidad de Santiago de Compostela). Santiago de Compostela, Spain

[8 ]Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil

[9 ]Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

[10 ]Neurology and Institute for Neurodegenerative diseases, Bordeaux University Hospital, and Bordeaux University, France

[11 ]Unité de Génétique Médicale, Bordeaux Hospital University Center, Bordeaux, France

[12 ]Division of Medicine, Buriram Hospital, Buriram, Thailand

[13 ]The Morton and Gloria Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Toronto, Canada

[14 ]Medical Genetics Group, School of Medicine & Dentistry, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, UK AB25 2ZD

[15 ]Translational Neuropharmacology, Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute and Department of Neurology, Karolinska Hospital, Huddinge, Stockholm, Sweden

[16 ]Department of Neurology, University of Michigan, Ann Arbor, MI, USA

[17 ]INSERM, Imagerie Cérébrale et Handicaps Neurologiques, Centre Hospitalier Universitaire de Toulouse, UMR 825, Pole Neurosciences, CHU Purpan, place du Dr Baylac, F-31059 Toulouse, France; Université de Toulouse, UPS, Toulouse, France

[18 ]Barrow Neurological Institute, Phoenix, AZ, USA

[19 ]Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genova, Italy

[20 ]Department of Neurology, Oregon Health & Science University, Portland, OR, USA

[21 ]Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium

[22 ]Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

[23 ]Department of Pediatrics, Children’s Hospital Colorado and the University of Colorado Denver, Aurora, CO, USA

[24 ]Department of Neurology, George Washington University Medical School, Washington, DC, USA

[25 ]Department of Research, Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France

[26 ]Department of Neurology, Rouen University Hospital, Rouen, France

Author notes

Corresponding authors: Jean-Luc Battini, PhD, Directeur de Recherche INSERM, Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, 1919, route de Mende, 34293 Montpellier Cedex 05 - France, Tel: +33 (0)4 34 35 96 40, Fax: +33 (0)4 34 35 96 34, jean-luc.battini@ 123456igmm.cnrs.fr , Giovanni Coppola, MD, Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry & Neurology, David Geffen School of Medicine, #3506C Gonda Neuroscience and Genetics Research Center, University of California Los Angeles, 695 Charles E. Young Dr. South, Los Angeles, CA 90095, Tel: (310) 794-4172, Fax: (310) 794-9613, gcoppola@ 123456ucla.edu

[§]

equal contribution

[27]

Current address: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA

[28]

Current address: Kaiser Permanente, Southern California Permanente Medical Group, Regional Reference Laboratories, Genetics Laboratory, Los Angeles, CA, USA

Article

Manuscript ID: NIHMS679154

DOI: 10.1038/ng.3289

PMC ID: 4516721

PubMed ID: 25938945

SO-VID: 62eccab5-7bcb-4665-bc94-163d7040b76c

History

Comments

Comment on this article

scite_

Cited by 91

See all cited by

Most referenced authors 381

See all reference authors

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

Read this article at

Abstract

Related collections

Genomic Prediction

Most cited references 23

The emerging importance of the SPX domain-containing proteins in phosphate homeostasis.

Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice.

Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 114

Cited by 91

Most referenced authors 381