Genetic linkage of the dentinogenesis imperfecta type III locus to chromosome 4q

Dentinogenesis imperfecta type III (DGI-III) is an autosomal-dominant disor der of dentin formation which appears in a tri-racial southern Maryland pop ulation known as the "Brandywine isolate". This disease has suggestive evid ence of linkage to the long arm of human chromosome 4 (LOD score of 2.0) in a family presenting with both juvenile periodontitis and DGI-III. The purp ose of this study was to screen a family presenting with only DGI-III to de termine if this locus was indeed on chromosome 4q. Furthermore, we wanted t o determine if DGI-III co-localized with dentinogenesis imperfecta type II (DGI-II), which has been localized to 4q21-q23. Therefore, a large kindred from the Brandywine isolate was identified, oral examination performed, and blood samples collected from 21 family members. DNA from this family was g enotyped with 6 highly polymorphic markers that span the DGI-II critical re gion of chromosome 4q. Analysis of the data yielded a maximum two-point LOD score of 4.87 with a marker for the dentin matrix protein 1 (DMPI) locus, a gene contained in the critical region for DGI-II. Our results demonstrate d that the DGI-III locus is on human chromosome 4q21 within a 6.6 cM region that overlaps the DGI-II critical region. These results are consistent wit h the hypothesis that DGI-II is either an allelic variant of DGI-III or the result of mutations in two tightly linked genes.