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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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Images of FAM20A−/− tooth #18.A: Photographs of #18 after cutting it sagitally. B: Photographs of a wild-type molar after cutting it sagitally. C: Photograph of #18 before sectioning. D: Occlusal view of #18 by photograph (top) and 3-D μ-CT image. E: 3-D μ-CT image of inside #18. Note the hollow area in the crown and the calcified pulp chamber. F: 3-D μ-CT image of #18. Note the shortness of the crown, which as apparently greatly diminished by resorption.
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pgen-1003302-g004: Images of FAM20A−/− tooth #18.A: Photographs of #18 after cutting it sagitally. B: Photographs of a wild-type molar after cutting it sagitally. C: Photograph of #18 before sectioning. D: Occlusal view of #18 by photograph (top) and 3-D μ-CT image. E: 3-D μ-CT image of inside #18. Note the hollow area in the crown and the calcified pulp chamber. F: 3-D μ-CT image of #18. Note the shortness of the crown, which as apparently greatly diminished by resorption.

Mentions: Four extracted secondary teeth from the proband of family 3 were provided to us for analyses (Figure S2). The “enamel” on the crowns was thin, soft and crusty, and only evident near the cervical margins. The teeth were smaller than normal and showed irregularities of root form. The area coronal to the root furcation was sometimes expanded, while the roots themselves were short, thin, and sometimes fused. Some parts of the roots showed pronounced concavities resembling a row of bites from an apple. A mesial-distal cut was made through #18, the mandibular left second molar (Figure 4A, 4C) and compared to the normal tooth (Figure 4B). Much of the mesial half of the crown had been resorbed and was only partially replaced by mineral, producing “hollow” areas on 3-D μCT images (Figure 4D–4F), while much of the pulp chamber was calcified.


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)

Images of FAM20A−/− tooth #18.A: Photographs of #18 after cutting it sagitally. B: Photographs of a wild-type molar after cutting it sagitally. C: Photograph of #18 before sectioning. D: Occlusal view of #18 by photograph (top) and 3-D μ-CT image. E: 3-D μ-CT image of inside #18. Note the hollow area in the crown and the calcified pulp chamber. F: 3-D μ-CT image of #18. Note the shortness of the crown, which as apparently greatly diminished by resorption.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1003302-g004: Images of FAM20A−/− tooth #18.A: Photographs of #18 after cutting it sagitally. B: Photographs of a wild-type molar after cutting it sagitally. C: Photograph of #18 before sectioning. D: Occlusal view of #18 by photograph (top) and 3-D μ-CT image. E: 3-D μ-CT image of inside #18. Note the hollow area in the crown and the calcified pulp chamber. F: 3-D μ-CT image of #18. Note the shortness of the crown, which as apparently greatly diminished by resorption.
Mentions: Four extracted secondary teeth from the proband of family 3 were provided to us for analyses (Figure S2). The “enamel” on the crowns was thin, soft and crusty, and only evident near the cervical margins. The teeth were smaller than normal and showed irregularities of root form. The area coronal to the root furcation was sometimes expanded, while the roots themselves were short, thin, and sometimes fused. Some parts of the roots showed pronounced concavities resembling a row of bites from an apple. A mesial-distal cut was made through #18, the mandibular left second molar (Figure 4A, 4C) and compared to the normal tooth (Figure 4B). Much of the mesial half of the crown had been resorbed and was only partially replaced by mineral, producing “hollow” areas on 3-D μCT images (Figure 4D–4F), while much of the pulp chamber was calcified.

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