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

• Published in: Nature genetics Vol. 47; no. 6; pp. 579 - 581
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2015; Nature Publishing Group
• Subjects: 13/44; 38/109; 38/23; 631/208/1516; 692/699/375/365; 82/80; Agriculture; Animal Genetics and Genomics; Biomedicine; Brain Diseases, Metabolic, Inborn - genetics; brief-communication; Calcification; Calcinosis - genetics; Calcium phosphates; Cancer Research; Development and progression; DNA Mutational Analysis; Endocrinology and metabolism; Female; Flow cytometry; Gene Function; Gene mutations; Genealogy; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genetics; Health aspects; HEK293 Cells; Human Genetics; Human health and pathology; Humans; Life Sciences; Ligands; Lod Score; Male; Medical imaging; Middle Aged; Mutation; Mutation, Missense; Nervous system diseases; Neurobiology; Neurodegenerative Diseases - genetics; Neurons and Cognition; Pedigree; Receptors, G-Protein-Coupled - genetics; Receptors, Virus - genetics; Stroke; Womens health
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3289

Jean-Luc Battini, Giovanni Coppola and colleagues identify XPR1 mutations in several families with primary brain calcification. They further show that these mutations alter phosphate export activity, implicating defective phosphate homeostasis in the etiology of this disease. 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.