Clinical and molecular evaluation of four patients with partial duplications of the long arm of chromosome 18

Abstract

Four individuals with partial duplications of the long arm of chromosome 18 were analyzed at the clinical, cytogenetic, and molecular levels. Two of the individuals had duplications of the long arm from 18q21.1-qter because of inheritance of an unbalanced translocation. Both of these individuals displayed the clinical phenotype characteristic of Edwards syndrome. Two other patients had de novo interstitial duplications of 18q but did not have a clinical diagnosis of Edwards syndrome. The extent of the duplicated material in each patient was determined initially by using cytogenetic analysis and subsequently with more detailed comparisons of the duplicated regions by using molecular probes derived from a chromosome 18-specific lambda phage library. The results demonstrated that one of the de novo interstitial duplications that did not result in the Edwards syndrome phenotype had a more proximal breakpoint than that of the partial duplications of the two patients with features of Edwards syndrome. These results suggest that a single critical region for Edwards syndrome in the proximal portion of 18q is unlikely.