Application of copy number variation sequencing combined with whole exome sequencing in prenatal left-right asymmetry disorders.

BACKGROUND

Left-right (LR) asymmetry disorders present a complex etiology, with genetic factors emerging as a primary contributor. This study aims to explore the genetic underpinnings of chromosomal variants and individual genes in fetuses afflicted with prenatal LR asymmetry disorder.

METHODS

Through a retrospective analysis conducted between 2020 and 2023 at Tongji Hospital, Huazhong University of Science and Technology, genetic outcomes of LR asymmetric disorder were scrutinized utilizing copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) methodologies.

RESULTS

With a combination of CNV-seq and WES, 5 fetuses in 17 patients with LR asymmetry had chromosomal or genetic variants. CNV-seq revealed a 16p11.2 microdeletion syndrome in a situs inversus fetus presenting pathogenic and a 2q36.3 microduplication syndrome in a fetus with Heterotaxy presenting a variant of uncertain significance (VUS). WES identified NM_198075.4:c.755del in the LRRC56 gene and NM_001454.4:c.865_868dup in the FOXJ1 gene in two situs inversus cases, along with two variants in DNAH5 in two other fetuses. Further bioinformatics scrutiny was conducted to assess the protein structure and function prediction of these variants, ultimately indicating their potential pathogenicity.

CONCLUSION

The study highlights that fetuses with LR asymmetric disorders may have copy number variants, underscoring the significance of mutations in LRRC56 and FOXJ1 in the development of LR asymmetry disorders.