TY - JOUR
T1 - Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification
AU - Nicolas, Gaël
AU - Pottier, Cyril
AU - Maltête, David
AU - Coutant, Sophie
AU - Rovelet-Lecrux, Anne
AU - Legallic, Solenn
AU - Rousseau, Stéphane
AU - Vaschalde, Yvan
AU - Guyant-Maréchal, Lucie
AU - Augustin, Jérôme
AU - Martinaud, Olivier
AU - Defebvre, Luc
AU - Krystkowiak, Pierre
AU - Pariente, Jérémie
AU - Clanet, Michel
AU - Labauge, Pierre
AU - Ayrignac, Xavier
AU - Lefaucheur, Romain
AU - Ber, Isabelle Le
AU - Frébourg, Thierry
AU - Hannequin, Didier
AU - Campion, Dominique
PY - 2013/1/8
Y1 - 2013/1/8
N2 - Objectives: To identify a new idiopathic basal ganglia calcification (IBGC)-causing gene. Methods: In a 3-generation familywith 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 unknownmutation 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. Conclusion: Mutations of PDGFRB further support the involvement of this biological pathway in IBGC pathophysiology.
AB - Objectives: To identify a new idiopathic basal ganglia calcification (IBGC)-causing gene. Methods: In a 3-generation familywith 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 unknownmutation 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. Conclusion: Mutations of PDGFRB further support the involvement of this biological pathway in IBGC pathophysiology.
UR - http://www.scopus.com/inward/record.url?scp=84873693930&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e31827ccf34
DO - 10.1212/WNL.0b013e31827ccf34
M3 - Article
C2 - 23255827
AN - SCOPUS:84873693930
SN - 0028-3878
VL - 80
SP - 181
EP - 187
JO - Neurology
JF - Neurology
IS - 2
ER -