Defining a New Candidate Gene for Amelogenesis Imperfecta: From Molecular Genetics to Biochemistry Blanca Urzu ´a • Ana Ortega-Pinto • Irene Morales-Bozo • Gonzalo Rojas-Alcayaga • Vı ´ctor Cifuentes Received: 22 February 2010 / Accepted: 23 July 2010 / Published online: 3 December 2010 Ó Springer Science+Business Media, LLC 2010 Abstract Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypo- calcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis im- perfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene. Keywords Molecular genetics Á Biochemistry Á Amelogenesis Á New candidate gene B. Urzu ´a Á I. Morales-Bozo Department of Physical and Chemical Sciences, Faculty of Dentistry, University of Chile, Santiago, Chile A. Ortega-Pinto Á G. Rojas-Alcayaga Department of Oral Pathology, Faculty of Dentistry, University of Chile, Santiago, Chile V. Cifuentes Department of Ecological Sciences, Faculty of Sciences, University of Chile, Santiago, Chile B. Urzu ´a (&) Facultad de Odontologı ´a, Universidad de Chile, Av. Sergio Livingstone Pohlhammer 943, Comuna de Independencia, Santiago, Chile e-mail: brurzua@gmail.com 123 Biochem Genet (2011) 49:104–121 DOI 10.1007/s10528-010-9392-6