CHARACTERIZATION OF THE BREAKPOINTS IN UNBALANCED T(5-11)(P15-P15) CONSTITUTIONAL CHROMOSOME TRANSLOCATIONS IN 2 PATIENTS WITH BECKWITH-WIEDEMANN-SYNDROME USING FLUORESCENCE IN-SITU HYBRIDIZATION

Although the majority of patients with Beckwith-Wiedemann syndrome (BW S) have a normal karyotype, the study of those rare patients with a cy togenetic abnormality has given considerable insight into the genetics of this condition. The karyotypic abnormalities found include partial chromosome duplications of paternal origin and maternally derived tra nslocations which usually involve the 11p15 region and provide one of the lines of evidence for the location of the BWS gene(s). Because the extent of the duplicated region in these patients is variable, the ph enotypic expression of BWS is presumably due to the presence of a comm on duplicated region. Two unrelated patients with BWS were both noted to have a similar unbalanced t(5;11)(p15;p14) translocation. The paren ts in both families were unaffected but both fathers carried a balance d translocation involving the same chromosomes. Since the extent and n ature of the duplication apparently determines the complex phenotypes seen in these patients, we undertook a detailed analysis of the extent of the triplicated region using fluorescent in situ hybrisation (FISH ). Despite having markedly different phenotypes and presenting in disi milar ways the two patients had apparently identical duplication break points.