An Incidental Detection of a Cryptic Complex Chromosome Rearrangement Found During NGS Based PGT-SR: A Case Report

Area of Science:

• Genetics
• Reproductive Medicine
• Genomic Analysis

Background:

• Complex chromosome rearrangements (CCRs) involve multiple breakpoints and can cause reproductive failure despite normal phenotypes.
• Couples with CCRs face challenges including recurrent miscarriages and in vitro fertilization (IVF) failures.
• Preimplantation genetic testing for structural rearrangements (PGT-SR) is crucial for managing CCRs.

Observation:

• A couple with a history of reproductive failure was referred for preimplantation genetic testing (PGT).
• Previous PGT attempts using fluorescence in situ hybridization (FISH) resulted in only one healthy child.
• The mother was initially identified as a carrier of a 2;6 translocation.

Findings:

• Next-generation sequencing (NGS)-based PGT identified a previously undetected cryptic 3-way translocation involving chromosomes 2, 6, and 12.
• FISH analysis confirmed the mother as a carrier of a balanced 46,XX,t(2;6;12)(p21;p25;p13) translocation.
• No healthy embryos were identified in the fifth IVF cycle using NGS-based PGT-SR.

Implications:

• NGS-based PGT-SR is a highly accurate method for detecting complex and cryptic chromosomal rearrangements.
• This advanced PGT-SR approach can improve the diagnosis of CCRs, guiding reproductive decisions.
• Accurate identification of CCRs through NGS-based PGT-SR is vital for couples experiencing recurrent reproductive failure.