PDGFB partial deletion: a new, rare mechanism causing brain calcification with leukoencephalopathy

J Mol Neurosci. 2014 Jun;53(2):171-5. doi: 10.1007/s12031-014-0265-z. Epub 2014 Mar 7.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Basal Ganglia Diseases / diagnosis
  • Basal Ganglia Diseases / genetics*
  • Calcinosis / diagnosis
  • Calcinosis / genetics*
  • Exons
  • Female
  • Gene Deletion*
  • Heterozygote
  • Humans
  • Leukoencephalopathies / diagnosis
  • Leukoencephalopathies / genetics*
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / genetics*
  • Proto-Oncogene Proteins c-sis / genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics


  • Proto-Oncogene Proteins c-sis
  • SLC20A2 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type III

Supplementary concepts

  • Fahr's disease