Amelogenesis imperfecta is a group of hereditary enamel defects. Of the autosomal dominant forms, only the local hypoplastic type has been mapped to human chromosome 4q 13-4q21.
Enamelin is a large enamel matrix
protein secreted by ameloblasts. The purpose of this study was to determine the human chromosomal localization of
enamelin to establish an association with various forms of
amelogenesis imperfecta. Chromosomal mapping was performed by polymerase chain reaction (PCR) amplification using somatic hybrid and deletion/derivation cell line panels with an
enamelin primer set based on 100% conserved regions between pig and mouse cDNAs. Sequence-tagged site content mapping using eight markers within the critical local hypoplastic
amelogenesis imperfecta region was then performed using an isolated human
enamelin genomic BAC clone. The human
enamelin amplicon was confirmed by DNA sequence analysis, revealing 81% and 73% identity to pig and mouse cDNAs, respectively. PCR amplification using a somatic cell hybrid panel placed
enamelin on chromosome 4 with analysis of a regional chromosome 4 mapping panel refining the localization to 4q 13.1-q21.23. An identified human
enamelin BAC genomic clone was shown to contain markers D4S2604 and D4S2670, as well as the first exon of the human ameloblastin gene, placing
enamelin in the critical
amelogenesis imperfecta locus between markers HIS1 and D4S2604 at 4q21. Our results suggest that
enamelin is a strong candidate gene for this disease. Furthermore, human 4q21 may contain a second cluster of enamel matrix genes located proximally to the identified cluster of dentin and bone genes.