title: FAM20A mutations can cause enamel-renal syndrome (ERS).
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.
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Wang
authors.forename: Parissa
authors.initials: P
authors.lastname: Aref
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hu
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Milkovich
authors.forename: James P
authors.initials: JP
authors.lastname: Simmer
authors.forename: Mohammad
authors.initials: M
authors.lastname: El-Khateeb
authors.forename: Hinda
authors.initials: H
authors.lastname: Daggag
authors.forename: Zaid H
authors.initials: ZH
authors.lastname: Baqain
authors.forename: Jan C-C
authors.initials: JC
authors.lastname: Hu
mesh_terms: D000567:Amelogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D003743:Dental Enamel / Q000378:metabolism / Q000473:pathology; D003746:Dental Enamel Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005351:Fibromatosis, Gingival / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006056:Golgi Apparatus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D009154:Mutation; D009397:Nephrocalcinosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D003746:Dental Enamel Proteins; C571509:FAM20A protein, human; D010770:Phosphotransferases