Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

Abstract

<b><i>Background/Aims:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> All patients had bi-allelic <i>FAM20A</i> mutations segregating with the disease; 20 different mutations were identified. <b><i>Conclusions:</i></b> This au-tosomal recessive disorder, also known as enamel renal syndrome, of <i>FAM20A</i> causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic <i>FAM20A</i> mutations will eventually show nephrocalcinosis.