Novel missense mutation of the FAM83H gene causes retention of amelogenin and a mild clinical phenotype of hypocalcified enamel Blanca Urzu ´a a,e, * , Carolina Martı ´nez a,e , Ana Ortega-Pinto b , Daniela Adorno b , Irene Morales-Bozo a , Gonzalo Riadi c , Lilian Jara d , Anita Plaza a , Claudia Lefimil a , Carla Lozano a , Monserrat Reyes b a Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N8 943, Independencia, Santiago, Chile b Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Sergio Livingstone Ave. N8 943, Independencia, Santiago, Chile c Center of Bioinformatics and Molecular Simulations, CBSM, Faculty of Engineering, University of Talca, 2 norte Ave. N8 685, Talca, Chile d Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia Ave. N8 1027, Santiago, Chile a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 1 3 5 6 – 1 3 6 7 a r t i c l e i n f o Article history: Received 27 February 2015 Received in revised form 10 June 2015 Accepted 11 June 2015 Keywords: Amelogenesis Missense mutation FAM83H gene Amelogenin retention Mild phenotype a b s t r a c t Objective: Amelogenesis imperfecta (AI) is a group of clinically and genetically heteroge- neous 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. Design: 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 immuno- histochemistry. 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 persis- tence of organic matter including amelogenins. * Corresponding author. Tel.: +56 2 29781793, +56 9 99134895. E-mail addresses: brurzua@gmail.com (B. Urzu ´ a), carolina_aml@yahoo.com (C. Martı´nez), aveortega@gmail.com (A. Ortega-Pinto), daniadorno@gmail.com (D. Adorno), irenemoralesbozo@gmail.com (I. Morales-Bozo), griadi@gmail.com (G. Riadi), ljara@med.uchile.cl (L. Jara), anitaplazaflores@yahoo.com (A. Plaza), claulefi@gmail.com (C. Lefimil), carlalozan@gmail.com (C. Lozano), montserrat.reyes.r@gmail.com (M. Reyes). e Equal authorship. Available online at www.sciencedirect.com ScienceDirect journal homepage: http://www.elsevier.com/locate/aob http://dx.doi.org/10.1016/j.archoralbio.2015.06.016 0003–9969/# 2015 Elsevier Ltd. All rights reserved.