Limits...
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.

Show MeSH

Related in: MedlinePlus

Family 2 from Jordan with FAM20A mutation c.720-2A>G; g.62232A>G; p.Q241_R271del.A: Pedigree: a dot marks person who donated samples for DNA sequencing. B: FAM20A intron 4 DNA sequencing chromatograms. The proband's parents (IV:1 and IV:2) were both heterozygous (R = A or G) at cDNA position 720 (2 arrowheads). The proband (V:5) had the c.720-2A>G transition mutation in both alleles of FAM20A. This mutation is predicted to cause the skipping of exon 5, which is predicted to delete 31 amino acids (Q241-R271) from the protein without shifting the reading frame. C: Proband's oral photo showing enamel hypoplasia, gingival enlargement and failed eruption. D: Proband's panoramic radiograph. Note the enamel hypoplasia, pulp calcifications, and unerupted teeth with pericoronal radiolucencies delimited by sclerotic borders. The left mandibular second molar (#18) shows apparent crown resorption. E: Ultrasound of proband's right kidney, located to the right of the yellow line.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3585120&req=5

pgen-1003302-g002: Family 2 from Jordan with FAM20A mutation c.720-2A>G; g.62232A>G; p.Q241_R271del.A: Pedigree: a dot marks person who donated samples for DNA sequencing. B: FAM20A intron 4 DNA sequencing chromatograms. The proband's parents (IV:1 and IV:2) were both heterozygous (R = A or G) at cDNA position 720 (2 arrowheads). The proband (V:5) had the c.720-2A>G transition mutation in both alleles of FAM20A. This mutation is predicted to cause the skipping of exon 5, which is predicted to delete 31 amino acids (Q241-R271) from the protein without shifting the reading frame. C: Proband's oral photo showing enamel hypoplasia, gingival enlargement and failed eruption. D: Proband's panoramic radiograph. Note the enamel hypoplasia, pulp calcifications, and unerupted teeth with pericoronal radiolucencies delimited by sclerotic borders. The left mandibular second molar (#18) shows apparent crown resorption. E: Ultrasound of proband's right kidney, located to the right of the yellow line.

Mentions: Family 2 was a consanguineous family from Jordan (Figure 2). A panorex radiograph of the proband showed the retention of primary teeth and delayed eruption of permanent cuspids, premolars, and second molars. No radiopaque enamel was detected and expanded peri-coronal radiolucencies were evident on all unerupted teeth. The pulp chambers were typically calcified and nearer the occlusal surface than expected. On some unerupted teeth the crown occlusal to the pulp chambers had disappeared, as if by resorption. An ultrasound of the proband's kidneys revealed bilateral medullary nephrosis with small calcifications in both kidneys causing acoustic shadowing. Otherwise both kidneys were normal in size and corticomedullary differentiation, each measuring about 11 cm in bipolar length.


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)

Family 2 from Jordan with FAM20A mutation c.720-2A>G; g.62232A>G; p.Q241_R271del.A: Pedigree: a dot marks person who donated samples for DNA sequencing. B: FAM20A intron 4 DNA sequencing chromatograms. The proband's parents (IV:1 and IV:2) were both heterozygous (R = A or G) at cDNA position 720 (2 arrowheads). The proband (V:5) had the c.720-2A>G transition mutation in both alleles of FAM20A. This mutation is predicted to cause the skipping of exon 5, which is predicted to delete 31 amino acids (Q241-R271) from the protein without shifting the reading frame. C: Proband's oral photo showing enamel hypoplasia, gingival enlargement and failed eruption. D: Proband's panoramic radiograph. Note the enamel hypoplasia, pulp calcifications, and unerupted teeth with pericoronal radiolucencies delimited by sclerotic borders. The left mandibular second molar (#18) shows apparent crown resorption. E: Ultrasound of proband's right kidney, located to the right of the yellow line.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1003302-g002: Family 2 from Jordan with FAM20A mutation c.720-2A>G; g.62232A>G; p.Q241_R271del.A: Pedigree: a dot marks person who donated samples for DNA sequencing. B: FAM20A intron 4 DNA sequencing chromatograms. The proband's parents (IV:1 and IV:2) were both heterozygous (R = A or G) at cDNA position 720 (2 arrowheads). The proband (V:5) had the c.720-2A>G transition mutation in both alleles of FAM20A. This mutation is predicted to cause the skipping of exon 5, which is predicted to delete 31 amino acids (Q241-R271) from the protein without shifting the reading frame. C: Proband's oral photo showing enamel hypoplasia, gingival enlargement and failed eruption. D: Proband's panoramic radiograph. Note the enamel hypoplasia, pulp calcifications, and unerupted teeth with pericoronal radiolucencies delimited by sclerotic borders. The left mandibular second molar (#18) shows apparent crown resorption. E: Ultrasound of proband's right kidney, located to the right of the yellow line.
Mentions: Family 2 was a consanguineous family from Jordan (Figure 2). A panorex radiograph of the proband showed the retention of primary teeth and delayed eruption of permanent cuspids, premolars, and second molars. No radiopaque enamel was detected and expanded peri-coronal radiolucencies were evident on all unerupted teeth. The pulp chambers were typically calcified and nearer the occlusal surface than expected. On some unerupted teeth the crown occlusal to the pulp chambers had disappeared, as if by resorption. An ultrasound of the proband's kidneys revealed bilateral medullary nephrosis with small calcifications in both kidneys causing acoustic shadowing. Otherwise both kidneys were normal in size and corticomedullary differentiation, each measuring about 11 cm in bipolar length.

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