Optical Genome Mapping for Prenatal Diagnosis in Fetuses With Structural Anomalies

To evaluate the clinical value of optical genome mapping (OGM) for prenatal diagnosis in fetuses with structural anomalies.

OGM was performed prospectively in 204 cases of fetuses with structural anomalies. Detection rates of OGM were investigated. Subgroup analysis was then conducted.

Overall, pathogenic or likely pathogenic (P/LP) chromosome aberrations were identified in 28 (13.7%) fetuses with structural anomalies using OGM, including 12 with numerical chromosomal abnormalities, 14 with P/LP copy number variations (CNVs) and two with balanced chromosomal rearrangements. OGM structural variation (SV) algorithm provided the structure and breakpoint information for 17 SVs and revealed six deletions, six tandem direct duplications, one inverted duplication, one paired duplication flanking a cryptic inversion and three balanced chromosomal rearrangements (one likely benign and two with breakpoints disrupting OMIM Morbid gene associated with dominant inheritance disorders). The diagnostic yields of OGM in the cystic hygroma group and multisystem malformation group were both significantly higher than those in other groups (35.7% vs. 10.3%, adjusted p = 0.018; 31.3% vs. 10.3%, adjusted p = 0.04).

Our study suggests that OGM is a reliable, comprehensive and high-resolution technology with an acceptable turnaround time that is a powerful method for prenatal diagnosis in fetuses with structural anomalies.