La Base Genética De Las Anomalías Heredadas De Los Dientes:

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European Journal of Medical Genetics 51 (2008) 273e291 http://www.elsevier.com/locate/ejmg

Review

The genetic basis of inherited anomalies of the teeth: Part 1: Clinical and molecular aspects of non-syndromic dental disorders
Isabelle Bailleul-Forestier a,*,1, Muriel Molla a,b,1, Alain Verloes c, Ariane Berdal b
b a PaediatricDentistry Department, Paris 7 University, AP-HP, Hotel-Dieu e Garanciere, Paris, France ˆ ` INSERM, UMRS 872, Molecular Oral Physiopathology, University Denis-Diderot Paris 7, Cordeliers Research Center, University Pierre et Marie Curie, Paris, France c Clinical Genetics Unit, Department of Medical Genetics, and INSERM U676, AP-HP, Hopital Robert Debre, ˆ ´ Paris, France

Received 22 October 2007;accepted 3 February 2008 Available online 26 March 2008

Abstract The genetic control of dental development represents a complex series of events, which can very schematically be divided in two pathways: specification of type, size and position of each dental organ, and specific processes for the formation of enamel and dentin. Several genes linked with early tooth positioning and development,belong to signalling pathways and have morphogenesis regulatory functions in morphogenesis of other organs where they are associated with the signalling pathways. Their mutations often show ple€ ıotropic effects beyond dental morphogenesis resulting in syndromic developmental disorders. Some genes affecting early tooth development (MSX1, AXIN2) are associated with tooth agenesis and systemic features(cleft palate, colorectal cancer). By contrast, genes involved in enamel (AMELX, ENAM, MMP20, and KLK4) and dentin (DSPP) structures are highly specific for tooth. Mutations in these genes have been identified as causes of amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasias and anomalies of teeth number (hypo-, oligo and anodontia), which only partially overlap with the classicalphenotypic classifications of dental disorders. This review of genetic basis of inherited

` * Corresponding author: UFR d’Odontologie, 5 rue Garanciere, 75006 Paris, France. Tel.: þ33 1 5310 5010; fax: þ33 1 5310 5111. E-mail address: isabelle.bailleul@univ-diderot-diderot.fr (I. Bailleul-Forestier). 1 These authors contributed equally to this work. 1769-7212/$ - see front matter Ó 2008 ElsevierMasson SAS. All rights reserved. doi:10.1016/j.ejmg.2008.02.009

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I. Bailleul-Forestier et al. / European Journal of Medical Genetics 51 (2008) 273e291

anomalies describes, in this first paper, the molecular bases and clinical features of inherited non-syndromic teeth disorders. And in a second part, the review focus on genetic syndromes with dental involvement. Ó 2008 Elsevier MassonSAS. All rights reserved.
Keywords: Genetics; Amelogenesis imperfecta; Dentinogenesis imperfecta; Oligodontia; Review

1. Introduction Advances in molecular genetics and the Human Genome Project have provided substantial progresses regarding the identification of genes involved in the pathogenesis of human diseases. These include dental diseases affecting enamel and dentin formation andanomalies in teeth number. Genetic diseases affecting tooth structure have been classified by the affected tissue (enamel versus dentin), by their specificity (syndromic versus non-syndromic) and their pattern of inheritance: autosomal dominant (AD), autosomal recessive (AR), or X-linked recessive (XLR). In this paper, we will review the clinical and molecular aspects of non-syndromic inherited dentaldisorders. A twin paper will focus on genetic syndromes with dental involvement. In human embryo, deciduous and permanent teeth develop from the oral ectoderm and the underlying neural mesenchymal cells, which have migrated from the cranial neural crest to the facial process. During the 6th week of human development, a line of oral epithelium cells thickens to form the dental lamina, which develops...