Breakpoint mapping uncovering about 1.32% of apparent balanced reciprocal translocation (ABRT) carriers existing cryptic complex chromosomal structural variations in preimplantation genetic testing (PGT)

To identify precise breakpoints, evaluate the reproduction-related risks and guide the following PGT treatment, high resolution breakpoint mapping was performed in ABRT carriers indicated by G-banding. A single-center, descriptive research. A large sample of 833 cases with ABRT who planned to accept PGT treatment were recruited in this study. For these patients, the approach of the next-generation sequencing following microdissection (MiroSeq) of the junction region in the derivative chromosomes, and linkage analysis of the adjacent single nucleotide polymorphisms (SNPs) were performed to distinguish the carriers from noncarriers in balanced embryos. For some cases with unbalanced chromosome rearrangement in the breakpoint region, SNP-array and fluorescence in situ hybridization (FISH) techniques were further used to determine the accurate karyotype. In the 833 cases with ABRT, we found 11 cases (1.32%) carried cryptic complex chromosomal structural variation, including 3 unbalanced chromosome rearrangements and 8 balanced ones in which 2 cases carried both inversion and translocation. In these 11 cases, 5 cases related to 3 chromosomes with 4 to 21 breakpoints and 6 cases involved 2 chromosomes with 3 to 6 breakpoints. It is noteworthy that there were two cases exhibited rare chromoanagenesis, including chromothripsis and chromoplexy. Fortunately, two couples have been both successfully transplanted a normal embryo and given birth to a healthy child, and the remaining nine cases are undergoing PGT treatment. In this large-scale analysis of ABRT, high resolution breakpoint mapping precisely characterized these breakpoints and uncovered 1.32% of the ABRT carriers existed cryptic complex chromosomal structural rearrangement. These data suggests that high resolution breakpoint mapping used in PGT can improve the accuracy of evaluating the reproduction-related risks and avoid genetic risks for the ABRT carriers.