Multiple technologies revealed complex chromosome rearrangements assembly and identified disrupted CNOT1 in fetus with ventriculomegaly.

The article focuses on the prenatal diagnosis and detailed genomic characterization of a fetus with ventriculomegaly caused by complex chromosome rearrangements (CCRs) involving chromosomes 4, 16, 18, and 21. Using a combination of optical genome mapping (OGM), Oxford Nanopore Technology (ONT) long-read sequencing, and trio-targeted next-generation sequencing (tNGS) haplotype linkage analysis, researchers identified multiple breakpoints disrupting the CNOT1 gene, resulting in a fusion gene with premature protein termination. The study highlights that integrating OGM's broad structural overview with ONT's detailed breakpoint resolution and tNGS haplotype data can effectively resolve CCR assemblies, which are challenging due to complex genomic rearrangements. This approach may improve the understanding and diagnosis of fetal chromosomal abnormalities associated with severe clinical phenotypes.