Abstract
Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS), which closely resembles ERS except for the renal calcifications. We characterized three families with AIGFS and identified, in each case, recessive FAM20A mutations: family 1 (c.992G>A; g.63853G>A; p.Gly331Asp), family 2 (c.720-2A>G; g.62232A>G; p.Gln241_Arg271del), and family 3 (c.406C>T; g.50213C>T; p.Arg136* and c.1432C>T; g.68284C>T; p.Arg478*). Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to ERS. By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A −/− molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres. Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a null mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.
Highlights
Enamel-Renal Syndrome (ERS; OMIM #204690) is a recessive syndrome characterized by severely hypoplastic or aplastic enamel on both the primary and secondary dentitions, pulp stones, and failed or delayed eruption of much of the permanent dentition, the posterior teeth
FAM20C phosphorylates secretory calcium-binding phosphoproteins (SCPPs) that are critical for bone, dentin, and enamel biomineralization, and other calciumbinding proteins in milk and saliva
All of the symptoms of AIGFS are found in enamel-renal syndrome (ERS, OMIM #204690), which in addition features kidney calcifications known as nephrocalcinosis
Summary
Enamel-Renal Syndrome (ERS; OMIM #204690) is a recessive syndrome characterized by severely hypoplastic (thin) or aplastic enamel on both the primary and secondary dentitions, pulp stones, and failed or delayed eruption of much of the permanent dentition, the posterior teeth. Coronal dentin is sometimes resorbed and replaced by lamellar bone and there is often hypercementosis on root surfaces. These dental symptoms are associated with nephrocalcinosis, blood chemistry analyses are typically normal [1,2,3]. The initial patient complaint is the lack of enamel and failed eruption of many permanent teeth. Subsequent reports found the kidney calcifications in patients with ERS to be benign [3,4,7]
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