GENETIC-HETEROGENEITY OF AUTOSOMAL-DOMINANT AMELOGENESIS IMPERFECTA DEMONSTRATED BY ITS EXCLUSION FROM THE AIH2 REGION ON HUMAN-CHROMOSOME 4Q

Amelogenesis imperfecta (AI) is a group of hereditary enamel defects, characterized by large clinical diversity. On the basis of differences in clinical manifestation and inheritance pattern, 14 different subty pes have been recognized. A locus for autosomal dominant AI (ADAI) of local hypoplastic type was recently mapped to the region between D4S39 2 and D4S395 on the long arm of chromosome 4. To test whether the chro mosome 4 locus is responsible for other forms of At as well, a linkage study was carried out with 17 families representing at least five cli nical forms of ADAI. Admixture tests for heterogeneity performed with the marker D4S2456 gave statistical support for genetic heterogeneity of ADAI with the odds 78:1. Linkage to the ADAI locus on chromosome 4q (AIH2) could only be demonstrated with families expressing the local hypoplastic type, and there was no support for heterogeneity within th at group of families. Furthermore, linkage could be excluded for five families with other clinical forms of ADAI. The data therefore demonst rated that ADAI is genetically heterogeneous, and that at least two lo ci for it exist. Copyright (C) 1996 Elsevier Science Ltd.