title: PDGFB partial deletion: a new, rare mechanism causing brain calcification with leukoencephalopathy.
abstract: Idiopathic basal ganglia calcification (IBGC) is a progressive cerebral disorder with diverse motor, cognitive, and psychiatric expression. It is inherited as an autosomal dominant trait. Three IBGC-causing genes have been identified in the past 2 years: SLC20A2, PDGFRB, and PDGFB. Biological and genetic evidence showed that loss of function of either SLC20A2 or the PDGFB/PDGFRB pathway was the mechanism underlying calcification in patients with a mutation. Recently, in a study focusing on SLC20A2, a large deletion at this locus was reported. No study has systematically searched for copy number variants (CNV) involving these three genes. We designed a quantitative PCR assay of multiple short fluorescent fragments (QMPSF) to detect CNVs involving one of these three genes in a single assay. Among the 27 unrelated patients from our IBGC case series with no mutation in SLC20A2, PDGFRB, and PDGFB, we identified in one patient a heterozygous partial deletion involving exons 2 to 5 of PDGFB. This patient exhibited both strio-pallido-dentate calcification and white matter hyperintensity of presumed vascular origin, associated with mood disorder, subtle cognitive decline, and gait disorder. We confirmed by RT-PCR experiments that the allele carrying the deletion was transcribed. The resulting cDNA lacks sequence for several critical functional domains of the protein. Intragenic deletion of PDGFB is a new and rare mechanism causing IBGC. CNVs involving the three IBGC-causing genes should be investigated in patients with no point mutation.
authors.affiliation: Inserm U1079, Rouen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
authors.forename: Anne
authors.initials: A
authors.lastname: Rovelet-Lecrux
authors.forename: Cyril
authors.initials: C
authors.lastname: Pottier
authors.forename: Olivier
authors.initials: O
authors.lastname: Martinaud
authors.forename: David
authors.initials: D
authors.lastname: Wallon
authors.forename: Louis
authors.initials: L
authors.lastname: Vernier
authors.forename: Gérard
authors.initials: G
authors.lastname: Landemore
authors.forename: Françoise
authors.initials: F
authors.lastname: Chapon
authors.forename: Carol
authors.initials: C
authors.lastname: Prieto-Morin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Tournier-Lasserve
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
mesh_terms: D000368:Aged; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000235:genetics*; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics
chemical_list: D020574:Proto-Oncogene Proteins c-sis; C493589:SLC20A2 protein, human; D050611:Sodium-Phosphate Cotransporter Proteins, Type III