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FAM20A mutations can cause enamel-renal syndrome (ERS).

Wang SK, Aref P, Hu Y, Milkovich RN, Simmer JP, El-Khateeb M, Daggag H, Baqain ZH, Hu JC - PLoS Genet. (2013)

Bottom Line: Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis.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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.

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 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.

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Scanning Electron Micrographs (SEMs) of mineral covering coronal dentin in a molar (#18) split for SEM examination.Left: Enamel layer in normal molar Right: Mineral covering dentin in FAM20−/− molar. No long thin crystals with rod/interrod organization are observed in the FAM20−/− molar.
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pgen-1003302-g006: Scanning Electron Micrographs (SEMs) of mineral covering coronal dentin in a molar (#18) split for SEM examination.Left: Enamel layer in normal molar Right: Mineral covering dentin in FAM20−/− molar. No long thin crystals with rod/interrod organization are observed in the FAM20−/− molar.

Mentions: SEM analysis of the occlusal surface of the FAM20A−/− mandibular second molar (tooth #18; Figure 5A) revealed a variety of surface features, including rough, knob-like calcifications (Figure 5B), dentin with exposed dentinal tubules (Figure 5C), some relatively smooth mineral near the dentin surface (Figure 5D), and pitted “enamel” mineral superficially resembling volcanic rock on the lateral aspect of the crown (Figure 5E–5F). SEMs of deliberately fractured areas showed no mineral organization characteristic of true enamel (Figure 6). SEMs of dentin looked the same as normal dentin (Figure 7). SEMs of the mandibular third molar (tooth #32; Figure 8A) showed a relatively smooth root surface (Figure 8B) perforated by small holes (dentinal tubules) and larger craters suggestive of resorption lacunae (Figure 8C–8E).


FAM20A mutations can cause enamel-renal syndrome (ERS).

Wang SK, Aref P, Hu Y, Milkovich RN, Simmer JP, El-Khateeb M, Daggag H, Baqain ZH, Hu JC - PLoS Genet. (2013)

Scanning Electron Micrographs (SEMs) of mineral covering coronal dentin in a molar (#18) split for SEM examination.Left: Enamel layer in normal molar Right: Mineral covering dentin in FAM20−/− molar. No long thin crystals with rod/interrod organization are observed in the FAM20−/− molar.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585120&req=5

pgen-1003302-g006: Scanning Electron Micrographs (SEMs) of mineral covering coronal dentin in a molar (#18) split for SEM examination.Left: Enamel layer in normal molar Right: Mineral covering dentin in FAM20−/− molar. No long thin crystals with rod/interrod organization are observed in the FAM20−/− molar.
Mentions: SEM analysis of the occlusal surface of the FAM20A−/− mandibular second molar (tooth #18; Figure 5A) revealed a variety of surface features, including rough, knob-like calcifications (Figure 5B), dentin with exposed dentinal tubules (Figure 5C), some relatively smooth mineral near the dentin surface (Figure 5D), and pitted “enamel” mineral superficially resembling volcanic rock on the lateral aspect of the crown (Figure 5E–5F). SEMs of deliberately fractured areas showed no mineral organization characteristic of true enamel (Figure 6). SEMs of dentin looked the same as normal dentin (Figure 7). SEMs of the mandibular third molar (tooth #32; Figure 8A) showed a relatively smooth root surface (Figure 8B) perforated by small holes (dentinal tubules) and larger craters suggestive of resorption lacunae (Figure 8C–8E).

Bottom Line: Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis.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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.

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 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.

Show MeSH
Related in: MedlinePlus