Primary familial brain calcification: Genetic analysis and clinical spectrum

Mov Disord. 2014 Nov;29(13):1691-5. doi: 10.1002/mds.26053. Epub 2014 Oct 4.

Abstract

Background: Primary familial brain calcification (PFBC) is a rare autosomal dominant disorder with bilateral calcification of basal ganglia and other cerebral regions, movement disorders, and neuropsychiatric disturbances. So far, three causative genes have been discovered: SLC20A2, PDGFRB and PDGFB, accounting for approximately 50% of cases.

Methods: Seven unrelated families with primary brain calcification were recruited to undergo clinical and genetic analysis, including Sanger sequencing of SLC20A2, PDGFRB, and PDGFB, and copy number analysis of SLC20A2.

Results: Mutations in SLC20A2 have been detected in three families: p.Glu368Glyfs*46, p.Ser434Trp, and p.Thr595Met. Intrafamilial phenotype variability has been observed. In spite of this, we found similar neuroimaging pattern among members of the same family.

Conclusions: This molecular analysis expands the mutational spectrum of SLC20A2, which remains the major causative gene of primary familial brain calcification, and suggests the existence of disease-causing mutations in at least another, still unknown gene.

Keywords: Fahr's disease; SLC20A2; brain calcification; primary familial brain calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Diseases / genetics*
  • Brain Diseases / pathology
  • Brain Diseases / physiopathology*
  • Calcinosis / genetics*
  • Calcinosis / pathology
  • Calcinosis / physiopathology*
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Radiography
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics*
  • Tomography Scanners, X-Ray Computed

Substances

  • SLC20A2 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type III