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

Leyla  Özer; Suleyman  Aktuna; Evrim  Unsal; Aysun  Baltaci; Volkan  Baltaci

doi:10.18502/jri.v23i4.10817

Leyla Özer Department of Medical Genetics, Faculty of Medicine, Yuksek İhtisas University, Ankara, Turkey
Suleyman Aktuna Department of Medical Genetics, Faculty of Medicine, Yuksek İhtisas University, Ankara, Turkey
Evrim Unsal Department of Medical Genetics, Faculty of Medicine, Yuksek İhtisas University, Ankara, Turkey
Aysun Baltaci Gen-Art IVF Center, Ankara, Turkey
Volkan Baltaci Department of Medical Genetics, Faculty of Medicine, Yuksek İhtisas University, Ankara, Turkey

DOI: https://doi.org/10.18502/jri.v23i4.10817

Keywords: Chromosomal translocation, Chromosome abnormalities, Next-generation sequencing, Preimplantation genetic testing.

Abstract

Background: Complex chromosome rearrangements (CCRs) involve more than 2 chromosomal breakpoints and cause the exchanges of chromosomal segments between two or more chromosomes. The carriers of CCRs have normal phenotypes, but they have a higher risk of reproductive failure.

Case Presentation: This paper presents a couple with a history of two affected children, one spontaneous abortion, three in vitro fertilization (IVF) failures, and one healthy boy who were referred to our laboratory for preimplantation genetic testing (PGT). The wife had been evaluated as a carrier of 46,XX,t (2;6)(p21;p25); therefore, four IVF treatment cycles supported with PGT for this translocation had been performed in different IVF centers until the couple consulted our laboratory. Only one of these four IVF attempts had resulted in a healthy boy and this IVF study had been performed with fluorescence in situ hybridization (FISH)-based preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR). The fifth IVF study with next-generation sequencing (NGS)-based PGT was performed by our laboratory and no healthy embryo was found in evaluated 6 embryos. During our NGS-based PGT, the cryptic involvement of 12p was firstly detected. FISH with chromosome 2,6, and 12 specific probes revealed that the mother was a carrier of a balanced 3-way translocation of 46,XX,t(2;6;12)(p21;p25;p13).

Conclusion: NGS based PGT-SR method is an accurate method for detecting the copy number variations and is helpful to find out the cryptic CCRs.