title: Novel missense mutation of the FAM83H gene causes retention of amelogenin and a mild clinical phenotype of hypocalcified enamel.
abstract: OBJECTIVE
  Amelogenesis imperfecta (AI) is a group of clinically and genetically heterogeneous inherited conditions, causing alterations in the structure of enamel and chemical composition of enamel matrix during development. The objective of this study was to compare the clinical, radiographic, histological and immunohistochemical phenotypes of subjects affected with hypocalcified AI from three Chilean families and identify causal mutations in the FAM83H gene.
  
  
  METHODS
  The diagnosis was made using clinical, radiographic, histological and genealogical data from the patients, who were evaluated according to the classification criteria by Witkop. PCR and Sanger sequencing of the complete coding sequence and surrounding intron regions of the FAM83H gene were conducted. The structural study of the affected teeth was performed with light microscopy, scanning electron microscopy and immunohistochemistry.
  
  
  RESULTS
  The probands of the three families were diagnosed with hypocalcified AI, but in only one of them the missense variant p.Gly557Cys was identified. This variant was not present in the SNP database or in 100 healthy controls and segregated with the disease in the affected family. Using light microscopy, a normal prismatic structure was observed in all three cases. However, the ultrastructure was found to be affected in two of the cases, showing persistence of organic matter including amelogenins.
  
  
  CONCLUSIONS
  These results suggest that FAM83H missense mutation reported in one of the families analyzed in this study might cause a phenotype of hypocalcified enamel more attenuated with retention of amelogenin.
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: brurzua@gmail.com.
authors.forename: Blanca
authors.initials: B
authors.lastname: Urzúa
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: carolina_aml@yahoo.com.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: aveortega@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega-Pinto
authors.affiliation: Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: daniadorno@gmail.com.
authors.forename: Daniela
authors.initials: D
authors.lastname: Adorno
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: irenemoralesbozo@gmail.com.
authors.forename: Irene
authors.initials: I
authors.lastname: Morales-Bozo
authors.affiliation: Center of Bioinformatics and Molecular Simulations, CBSM, Faculty of Engineering, University of Talca, 2 norte Ave. N° 685, Talca, Chile. Electronic address: griadi@gmail.com.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Riadi
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia Ave. N° 1027, Santiago, Chile. Electronic address: ljara@med.uchile.cl.
authors.forename: Lilian
authors.initials: L
authors.lastname: Jara
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: anitaplazaflores@yahoo.com.
authors.forename: Anita
authors.initials: A
authors.lastname: Plaza
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: claulefi@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lefimil
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: carlalozan@gmail.com.
authors.forename: Carla
authors.initials: C
authors.lastname: Lozano
authors.affiliation: Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N° 943, Independencia, Santiago, Chile. Electronic address: montserrat.reyes.r@gmail.com.
authors.forename: Monserrat
authors.initials: M
authors.lastname: Reyes
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D053523:Amelogenin / Q000235:genetics*; D002677:Chile; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D053523:Amelogenin; C527308:FAM83H protein, human; D011506:Proteins
keywords: Amelogenesis; Amelogenin retention; FAM83H gene; Mild phenotype; Missense mutation