Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta

Abstract

Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

Figure 1

Clinical phenotype and pedigree of Family 1. Family 1: A phenotype demonstrating generalized yellow-brown discoloration of the dentition (A1 patient III-2, A2 patient III-5); B X-ray showing lack of enamel opacity and a pathological loss of enamel (B1 patient III-2, B2 patient III-5); C pedigree of Family 1.

Figure 2

Clinical phenotype and pedigree of Family 2. Family 2: A phenotype of patient III-4 demonstrating points of yellow-brown discoloration of the dentition, and areas with thin enamel. (A1 dentition, A2 detail); B radiographic patient III-4; C pedigree of Family 2 suggested X-link AI.

Figure 3

A single nucleotide polymorphism in amelotin gene: change of A to G in base 7125 (NCBI35:4:71564458:71579819:1).