MOLECULAR CHARACTERIZATION AND DELINEATION OF SUBTLE DELETIONS IN DE-NOVO BALANCED CHROMOSOMAL REARRANGEMENTS

To test the hypothesis that the phenotypic abnormalities seen in cases with apparently balanced chromosomal rearrangements are the result of the presence of cryptic deletions or duplications of chromosomal mate rial near the breakpoints, we analyzed three cases with apparently bal anced chromosomal rearrangements and phenotypic abnormalities. We char acterized the breakpoints in these cases by using microsatellite analy sis by polymerase chain reaction and fluorescence in situ hybridizatio n analysis of yeast artificial chromosome clones selected from the bre akpoint regions. Molecular characterization of the translocation break point in patient 1 [46,XY,t(2;6)(p22.2;q23.1)] showed the presence of a 4- to 6-Mb cryptic deletion between markers D6S412 and D6S1705 near the 6q23.1 breakpoint. Molecular characterization of the proximal inve rsion 7q22.1 breakpoint in patient 2 [46,XY,inv(7)(q22.1q32.1)] reveal ed the presence of a 4-Mb cryptic deletion between D7S651 and D7S515 m arkers. No deletion or duplication of chromosomal material was found n ear the breakpoints in patient 3 [46,XX,t(2;6)(q33.1;p12.2)]. Our stud y suggests that a systematic molecular study of breakpoints should be carried out in cases with apparently balanced chromosomal rearrangemen ts and phenotypic abnormalities, because cryptic deletions near the br eakpoints may explain the phenotypic abnormalities in these cases.