title: Identification of partial SLC20A2 deletions in primary brain calcification using whole-exome sequencing.
abstract: Primary brain calcification (PBC) is a dominantly inherited calcifying disorder of the brain. SLC20A2 loss-of-function variants account for the majority of families. Only one genomic deletion encompassing SLC20A2 and six other genes has been reported. We performed whole-exome sequencing (WES) in 24 unrelated French patients with PBC, negatively screened for sequence variant in the known genes SLC20A2, PDGFB, PDGFRB and XPR1. We used the CANOES tool to detect copy number variations (CNVs). We detected two deletions of exon 2 of SLC20A2 in two unrelated patients, which segregated with PBC in one family. We then reanalyzed the same series using a QMPSF assay including one amplicon in each exon of SLC20A2 and detected two supplemental partial deletions in two patients: one deletion of exon 4 and one deletion of exons 4 and 5. These deletions were missed by the first screening step of CANOES but could finally be detected after readjustment of bioinformatic parameters and use of a genotyping step of CANOES. This study reports the first partial deletions of SLC20A2 and strengthens its position as the major PBC-causative gene. It is possible to detect short CNVs from WES data, although the sensitivity of such tools should be evaluated in comparison with other methods.
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: David
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil.|Biological Sciences Graduate Program, Federal University of Pernambuco, Recife, Brazil.
authors.forename: Joana
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Quenez
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Rovelet-Lecrux
authors.affiliation: Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Richard
authors.affiliation: Department of Neurology, Pontchaillou Hospital, Rennes University Hospital, Rennes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Vérin
authors.affiliation: Department of Neurology, Perpignan Hospital, Perpignan, France.
authors.forename: Snejana
authors.initials: S
authors.lastname: Jurici
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1127, CNRS UMR 7225, ICM, Paris, France.|AP-HP, Hôpital de la Pitié-Salpêtrière, Centre de Référence des Démences Rares, Paris, France.|AP-HP, Département des maladies du système nerveux, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil.|Department of Neuropsychiatry, Federal University of Pernambuco, Recife, Brazil.
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Mendes de Oliveira
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.|Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Department of Research, Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
mesh_terms: D000368:Aged; D000465:Algorithms; D001927:Brain Diseases / Q000175:diagnosis / Q000235:genetics*; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA / Q000379:methods; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics*; D013577:Syndrome; D000089842:Xenotropic and Polytropic Retrovirus Receptor
chemical_list: C493589:SLC20A2 protein, human; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor