Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Nephron Physiol. 2012;122(1-2):1-6. doi: 10.1159/000349989. Epub 2013 Feb 23.


Background/aims: Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood.

Methods: We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing.

Results: All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified.

Conclusions: This autosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amelogenesis Imperfecta / complications
  • Amelogenesis Imperfecta / genetics*
  • Amelogenesis Imperfecta / pathology
  • Child
  • Consanguinity
  • Dental Enamel Proteins / genetics*
  • Exome / genetics
  • Family Health
  • Female
  • Genes, Recessive / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Nephrocalcinosis / complications
  • Nephrocalcinosis / genetics*
  • Nephrocalcinosis / pathology
  • Pedigree
  • Sequence Analysis, DNA / methods
  • Syndrome
  • Young Adult


  • Dental Enamel Proteins
  • FAM20A protein, human