Integrating Optical Genome Mapping With Conventional Methods in Families Seeking Genetic Counseling

This study aimed to evaluate the clinical value of integrating optical genome mapping (OGM) with conventional genetic methods in the diagnosis of families with spontaneous abortion or offspring abnormalities.

Herein, 24 families were included. Genetic testing was first applied in fetuses and children according to indications if samples were available. A parental study was then conducted using OGM with or without conventional methods.

In total, 76 samples (28 samples of fetuses and children from 20 families and 48 samples of all 24 parents) were investigated. Clinically reported variants were identified in 21 (21/28, 75.0%) fetuses and children from 17 (17/20, 85.0%) families. OGM with or without conventional methods detected 16 (16/24, 66.7%) clinically reported variants in either parent, including five submicroscopic balanced translocations, two microscopic balanced translocations, four complex chromosomal rearrangements, two D4Z4 repeat contraction disorders, and three variants of uncertain significance (VOUS). Additionally, variations detected in fetuses and children from three (3/24, 12.5%) families were determined to be de novo by OGM. OGM identified structural variations (SVs) out of the detection range of conventional methods and provided structure and breakpoint information to improve clinical interpretation.

This study illustrates that integrating OGM with conventional methods is a feasible and powerful strategy in families with spontaneous abortion or offspring abnormalities.