Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature.

The amelogenesis imperfectas (AI) are a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Although X-linked, autosomal dominant and autosomal recessive forms of AI have been clinically characterized, only two genes (AMELX and ENAM) have been associated with AI. To date, three enamelin (ENAM) mutations have been identified. These mutations cause phenotypically diverse forms of autosomal dominant AI. Detailed phenotype-genotype correlations have not been performed for autosomal dominant AI due to ENAM mutations. We identified a previously unreported kindred segregating for the ENAM mutation, g.8344delG. Light and electron microscopy analyses of unerupted permanent teeth show the enamel is markedly reduced in thickness, lacks a prismatic structure and has a laminated appearance. Taken together these histological features support the enamelin protein as being critical for the development of a normal enamel thickness and that it likely has a role in regulating c-axis crystallite growth. Because there is growing molecular and phenotypic diversity in the enamelin defects, it is critical to have a nomenclature and numbering system for characterizing these conditions. We present a standardized nomenclature for ENAM mutations that will allow consistent reporting and communication.