Multisite evaluation and validation of Optical Genome Mapping for prenatal genetic testing

Abstract

Cytogenetic studies represent a critical component of prenatal genetic testing. Prenatal diagnostic testing of amniotic fluid, chorionic villus sampling, or more rarely, fetal cord blood, is recommended following a positive or unreportable NIPT, maternal serum screen, abnormal ultrasound or increased genetic risk based on family history. While chromosomal microarray is the recommended first-tier prenatal diagnostic test for the detection of sub-microscopic copy number variants, in practice, multiple assays are often assessed, in concert, to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenetic aberrations detectable by karyotyping, FISH, and microarray. In an effort to characterize the potential of optical genome mapping as a novel alternative to conventional testing, a multi-site, multi-operator, multi-instrument clinical research study was conducted to demonstrate its analytic validity and clinical utility. In the first phase a total of 200 specimens representing 123 unique cases demonstrated 100% concordance with standard of care methods and 100% reproducibility between sites, operators, and instruments. Analysis and interpretation of cases with incidental findings of potential clinical significance also were performed.