Molecular biology of hereditary enamel defects

Amelogenesis imperfecta is a disfiguring inherited condition affecting tooth enamel. X-Linked and autosomal dominant and recessive inheritance patterns occur. X-Linked amelogenesis imperfecta has been studied extensively at the molecular level. Linkage analysis has shown that there is genetic hetetogeneity in X-linked amelogenesis imperfecta with two identified loci: AIH1 and AIH3. The AIH1 locus corresponds to the location of the amelogenin gene on the distal short arm of the X chromosome; various mutations in the amelogenin gene have been found in families with X-linked amelogenesis imperfecta. The AIH3 locus maps to the Xq24-q27.1 region on the long arm of the X chromosome. Linkage to the long arm of chromosome 4 has been established in three families with autosomal dominant amelogenesis imperfecta. There is as yet no published evidence for genetic heterogeneity in autosomal dominant amelogenesis imperfecta as in X-linked amelogenesis imperfecta. Candidate genes for autosomal dominant amelogenesis imperfecta include tuftelin (1q), albumin (4q) and ameloblastin (4q) but the involvement of these genes in the disease has yet to be demonstrated. In view of the variable clinical appearances within families with autosomal dominant amelogenesis imperfecta and X-linked amelogenesis imperfecta, together with the finding that different X-linked amelogenesis imperfecta phenotypes result from mutations within the same gene, an alternative classification based on the molecular defect and mode of inheritance rather than phenotype has been proposed.