Fluorescence in situ Hybridization Analysis Can Reveal Subtle Chromosomal Rearrangements in Pericentromeric Regions of Acrocentric Chromosomes in Patients with Reproductive Failure.

Introduction: Infertility and recurrent pregnancy loss are serious health problems often associated with genetic abnormalities such as chromosomal rearrangements. Although conventional cytogenetics plays a crucial role in this kind of diagnostics, it fails to detect submicroscopic changes, especially in the pericentromeric regions of acrocentric chromosomes, which are potentially prone to rearrangement. To overcome this limitation, this study aimed to identify such subtle changes that can lead to reproductive disorders using fluorescence in situ hybridization (FISH) technique and newly developed fluorescence probes that specifically target these regions.

Methods: The study group consisted of 50 couples who, despite having unprotected sexual intercourse, had been unable to conceive for more than a year or had suffered two or more miscarriages and had been unable to carry a pregnancy to term. After exclusion of cytogenetically visible chromosomal alterations, patients were subjected to FISH analysis with three newly designed probe sets that stain the centromere and pericentromere regions of acrocentric chromosomes 13 and 21 (SET-I), 14 and 22 (SET-II), and 15 (SET-III).

Results: FISH analysis of SET-II and SET-III probes revealed a cryptic reciprocal translocation between chromosomes 15 and 22 in a 33-year-old male. His female cousin was also found to be a carrier of the same translocation and had a dysmorphic child due to adjacent II missegregation.

Conclusion: Subtle chromosomal changes, such as reciprocal translocations in our patients, may be one of the underlying causes of unbalanced gametes in reproductive disorders. The use of three newly designed FISH probe sets may need to be considered to offer comprehensive prenatal and preimplantation genetic testing to couples with reproductive failure.