Update and Mutational Analysis of SLC20A2: A Major Cause of Primary Familial Brain Calcification

Hum Mutat. 2015 May;36(5):489-95. doi: 10.1002/humu.22778. Epub 2015 Apr 6.


Primary familial brain calcification (PFBC) is a heterogeneous neuropsychiatric disorder, with affected individuals presenting a wide variety of motor and cognitive impairments, such as migraine, parkinsonism, psychosis, dementia, and mood swings. Calcifications are usually symmetrical, bilateral, and found predominantly in the basal ganglia, thalamus, and cerebellum. So far, variants in three genes have been linked to PFBC: SLC20A2, PDGFRB, and PDGFB. Variants in SLC20A2 are responsible for most cases identified so far and, therefore, the present review is a comprehensive worldwide summary of all reported variants to date. SLC20A2 encodes an inorganic phosphate transporter, PiT-2, widely expressed in various tissues, including brain, and is part of a major family of solute carrier membrane transporters. Fifty variants reported in 55 unrelated patients so far have been identified in families of diverse ethnicities and only few are recurrent. Various types of variants were detected (missense, nonsense, frameshift) including full or partial SLC20A2 deletions. The recently reported SLC20A2 knockout mouse will enhance our understanding of disease mechanism and allow for screening of therapeutic compounds. In the present review, we also discuss the implications of these recent exciting findings and consider the possibility of treatments based on manipulation of inorganic phosphate homeostasis.

Keywords: Fahr's disease; SLC20A2; basal ganglia; brain calcification.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Brain Diseases / diagnosis
  • Brain Diseases / genetics*
  • Brain Diseases / pathology*
  • Calcinosis / genetics*
  • DNA Mutational Analysis
  • Exons
  • Genetic Association Studies
  • Genetic Variation
  • Humans
  • Mutation*
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type III / metabolism


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