AMELOBLASTIN GENE (AMBN) MAPS WITHIN THE CRITICAL REGION FOR AUTOSOMAL-DOMINANT AMELOGENESIS IMPERFECTA AT CHROMOSOME 4Q21

Amelogenesis imperfecta (AI) is a broad group of hereditary enamel def ects that is characterized by a high degree of clinical diversity. Rec ently, the local hypoplastic form of autosomal dominant AI (AIH2) has been mapped to human chromosome 4q in a 17.6-cM, region. This locus ha s been further refined to a 4-Mb interval between D4S2421 and Albumin. Recently, a cDNA clone for an enamel matrix protein, ameloblastin (AM BN), has been isolated. In this report, we have isolated a PAC human g enomic clone containing the human AMBN gene. The AMBN was mapped by tw o color fluorescence in situ hybridization using two P1 genomic clones for sequence-tagged site (STS) markers, D4S400 and D4S409, which flan k the critical AIH2 region. Our results place AMBN at 4q21 between D4S 409 (4q13) and D4S400 (4q21), Furthermore, the AMBN PAC genomic clone was shown to contain three STS markers, D4S2604, D4S2670, and D4S2609, which are contained within the critical region defined by six Swedish families with AIH2. AMBN is therefore a strong candidate gene for AIH 2. (C) 1997 Academic Press.