Associations between the clinical findings of cases having submicroscopic chromosomal imbalances at chromosomal breakpoints of apparently balanced structural rearrangements

Abstract Although the carriers with apparently balanced structural rearrangements have usually normal phenotype, phenotypical abnormalities can be seen in approximately 6% de novo cases. A number of different mechanisms are involved in the appearance of these phenotypic abnormalities, one of which is submicroscopic chromosomal imbalances at chromosomal breakpoints. Our goal was to unravel the possible submicroscopic chromosomal imbalances at chromosomal breakpoints by using array-CGH analysis in patients with apparently balanced structural rearrangements and to link these to the clinical findings. A total of nine patients with reciprocal translocation carriers (2 familial, 7 de novo ) and six patients with inversion carriers (2 familial, 4 de novo ) were included in this study. In order to evaluate the possible microdeletions and microduplications at the chromosomal breakpoints, DNA samples were isolated from the peripheral blood of the patients (and their parents) and investigated using array-CGH analysis. Array-CGH analysis revealed submicroscopic chromosomal imbalances at breakpoints in 3 of the 7 (43%) de novo reciprocal translocation carriers. Additionally, 1 out of 4 (25%) de novo inversion carriers were found to have a submicroscopic chromosomal imbalance in unrelated chromosome seen in cytogenetic analysis. Furthermore, no submicroscopic chromosomal imbalances were detected in either of the two familially transmitted reciprocal translocation carriers. Based on the results of both array-CGH analysis and conventional cytogenetic analysis, the karyotypes of the patients were designated as follows: 46,XY,t(13;16)(q14;q12.1)dn.arr[hg19]13q14.2-q21.1(50,131,521–57,306,322)x1dn; 46,XY,t(6;9)(q13;p12)dn.arr[hg19]6q14.1(78,016,882–83,293,127),9p23p22.3(12,249,507–15,939,627)x1dn; 46,XX,t(X;16)(p11.21;p11.2)dn.arr[hg19]Xp11.22(50,367,783–50,441,087)x3dn; 46,XX,inv.(18)(p11.23q11.2)dn.arr[hg19]22q11.21(18,706,001–21,505,417)x1mat. Our results demonstrate the necessity of using array-CGH to evaluate patients with apparently balanced structural rearrangements in order to determine the submicroscopic chromosomal imbalances at chromosomal breakpoints that are related to the observed clinical abnormalities.