title: Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification.
abstract: OBJECTIVE
  To identify a new idiopathic basal ganglia calcification (IBGC)-causing gene.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Mutations of PDGFRB further support the involvement of this biological pathway in IBGC pathophysiology.
authors.affiliation: Inserm U1079, University Hospital and Faculty of Medicine, Rouen.
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
authors.forename: Cyril
authors.initials: C
authors.lastname: Pottier
authors.forename: David
authors.initials: D
authors.lastname: Maltête
authors.forename: Sophie
authors.initials: S
authors.lastname: Coutant
authors.forename: Anne
authors.initials: A
authors.lastname: Rovelet-Lecrux
authors.forename: Solenn
authors.initials: S
authors.lastname: Legallic
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rousseau
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vaschalde
authors.forename: Lucie
authors.initials: L
authors.lastname: Guyant-Maréchal
authors.forename: Jérôme
authors.initials: J
authors.lastname: Augustin
authors.forename: Olivier
authors.initials: O
authors.lastname: Martinaud
authors.forename: Luc
authors.initials: L
authors.lastname: Defebvre
authors.forename: Pierre
authors.initials: P
authors.lastname: Krystkowiak
authors.forename: Jérémie
authors.initials: J
authors.lastname: Pariente
authors.forename: Michel
authors.initials: M
authors.lastname: Clanet
authors.forename: Pierre
authors.initials: P
authors.lastname: Labauge
authors.forename: Xavier
authors.initials: X
authors.lastname: Ayrignac
authors.forename: Romain
authors.initials: R
authors.lastname: Lefaucheur
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001120:Arginine; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000473:pathology; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D030541:Databases, Genetic; D059472:Exome; D005260:Female; D006801:Humans; D007930:Leucine; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000150:complications; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011392:Proline; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014364:Tryptophan
chemical_list: D014364:Tryptophan; D001120:Arginine; D011392:Proline; D020797:Receptor, Platelet-Derived Growth Factor beta; D007930:Leucine