Optical genome mapping as a diagnostic tool for unsolved balanced translocations in couples with adverse pregnancy outcomes: a case series

TL;DR

Optical genome mapping helps identify hidden genetic translocations in couples with pregnancy issues, enabling better diagnosis and counseling.

Contribution

OGM successfully detects cryptic balanced translocations missed by traditional methods in cases of adverse pregnancy outcomes.

Findings

OGM identified precise cryptic balanced translocations in three unsolved cases.

OGM defined genomic breakpoints at high resolution, including a Yp11.2 translocation in a 46,XX SRY+ male.

OGM provides a molecular diagnosis for reproductive risk assessment and genetic counseling.

Abstract

Cryptic balanced translocations are a challenging diagnostic dilemma in conventional cytogenetics. This study aimed to evaluate the utility of optical genome mapping (OGM), an emerging technology for detecting structural variations, in resolving such cases among couples with adverse pregnancy outcomes.

We performed a retrospective analysis using OGM on three unsolved cases following karyotyping and trio-whole exome sequencing (trio-WES). The cohort included two couples with adverse pregnancy outcomes and a 46,XX SRY+ male.

In all three cases where a translocation was clinically suspected but cytogenetically elusive, OGM successfully identified precise cryptic balanced translocations. Crucially, it defined the genomic breakpoints at high resolution. In the case of the 46,XX SRY+ male, OGM identified a cryptic translocation of Yp11.2 into Xp22.3 and the paracentric inversion inv(Y)(p11.2p11.2), explaining the sex reversal phenotype.

This study shows that OGM is a valuable adjunctive diagnostic method for detecting cryptic translocations. By providing a molecular diagnosis, it enables definitive reproductive risk assessment and personalized genetic counseling for carrier couples.

The online version contains supplementary material available at 10.1186/s40001-025-03814-7.

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