Multi-technical validation reveals the origin of a de novo mutation in the offspring of a Robertsonian translocation der(13;14)(q10;q10) carrier after preimplantation genetic testing for structural rearrangements

Objective: To explore the origin of the translocation in the offspring of a male carrier of Robertsonian translocation der(13;14)(q10;q10) using preimplantation genetic testing for structural rearrangements (PGT-SR) combined with multiple techniques. The study also examines the associated risks and insights derived from PGT-SR. Methods: A male carrier of Robertsonian translocation der(13;14)(q10;q10) underwent assisted conception using PGT-SR. During the screening process, normal embryos were selected for transfer, resulting in a successful pregnancy. Prenatal diagnosis and postnatal peripheral blood karyotype analysis confirmed that the offspring carried the same Robertsonian translocation. The origin of the mutation was further verified using multiple techniques, including chromosomal microdissection and chromosome conformation–based karyotyping (C-MoKa). Results: Review of the PGT-SR process and kinship numerical affinity analysis confirmed that the embryo biopsy sample and the offspring were genetically identical, thereby excluding the possibility of sample misidentification during the procedures. Chromosomal microdissection revealed that the Robertsonian translocation in the offspring did not correspond to the male carrier’s translocated chromatid, suggesting the presence of a novel translocation. Using the innovative C-MoKa approach, the origin of the translocation was traced to the non-translocated chromosomes of both parents, conclusively confirming a de novo mutation. Conclusion: This study integrated quantitative kinship analysis, chromosomal microdissection, and C-MoKa technology. For the first time, the occurrence of de novo isovariant events within Robertsonian translocations was successfully validated, providing valuable reference evidence for genetic counseling prior to PGT-SR.