Hidden translocation between 15qter and 18qter impressed during cycles of preimplantation genetic testing using linkage analyses and chromosome microarray subsequently verified by fluorescence in situ hybridization.

OBJECTIVE: Hidden translocations (HTs) are balanced chromosomal exchanges that evade detection by conventional cytogenetic analyses. Their clinical identification is challenging but may be inferred from atypical findings of preimplantation genetic testing (PGT).

CASE REPORT: PGT was performed for a family with multiple congenital anomalies and recurrent pregnancy loss, in which only a 3.6 Mb deletion at 11p15.1p14.3 of uncertain clinical significance and a clinically relevant 2.9 Mb deletion at 15q26.1 in the affected father were initially identified. Linkage analysis focusing on the 15q26.1 deletion revealed an atypical allele segregation pattern. Meanwhile, array comparative genomic hybridization (aCGH) repeatedly detected a 15q26.2q26.3 duplication together with an 18q22.3q23 deletion in embryos, suggesting a parental HT involving 15qter and 18qter. Fluorescence in situ hybridization (FISH) subsequently confirmed a HT occurring in cis with the paternal 15q26.1 deletion.

CONCLUSION: This case illustrates how integrating PGT findings with parental analyses can reveal cryptic structural rearrangements. The combined use of linkage analysis and aCGH enabled accurate detection of embryo aneuploidies and structural variants, helping prevent the transmission of pathogenic alterations and improving reproductive outcomes.