Analysis of human enamel genes: insights into genetic disorders of enamel.

A number of inherited craniofacial diseases are known to be associated with gene mutations. Inherited genetic disorders of enamel formation called amelogenesis imperfecta (AI) affect the human population with a prevalence of 1 in 14,000 in the United States. Amelogenins, the major proteins in developing enamel matrix of mammalian teeth, have been suggested to participate in normal enamel matrix biomineralization, as well as with abnormal biomineralization such as seen in AI. The complementary DNA for mouse amelogenin gene (AMEL) has been cloned, characterized, and used as a probe to establish the chromosomal locations of AMEL for mouse and man. The human AMEL gene sequences have been located to the distal short arm p22.1----p22.3 region of the X chromosome, and the pericentromeric region of the Y chromosome. An assignment of human AMEL gene to the X chromosome p22 region together with a recent assignment of the X-linked AI disease locus to the Xp22.2 region support the association of the AMEL-X gene with AI. This also leads us to propose that a mutated AMEL-X gene produces altered amelogenin polypeptide, which is defective in its ability to participate in mineralization of enamel matrix, thus giving rise to the X-linked phenotypes of AI.