Advancements in Pathogenic Genes and Biomarkers for Non-syndromic Cleft Lip With or Without Cleft Palate Via Multiomics.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common congenital malformation influenced by a combination of environmental and genetic factors. nsCL/P is usually diagnosed using fetal ultrasound during the late second trimester; however, these results are often affected by factors such as instruments, fetal position, and maternal obesity. Moreover, by this time, structural anomalies in the fetuses are already formed and missed optimal time for intervention. Therefore, identifying more efficient and non-invasive biomarkers before fetal ultrasound is essential. In recent years, rapidly evolving omics technologies, including genomics, transcriptomics, proteomics, lipidomics, epigenomics, and single-cell omics, have been used to identify several nsCL/P-associated risk genes. Additionally, omics technologies have proven invaluable for investigating non-invasive biomarkers for prenatal diagnosis of nsCL/P. Therefore, this article reviews the current applications of multi-omics technologies in nsCL/P research, focusing on their use to identify pathogenic genes and the research advances in prenatal diagnosis. We highlighted the technological landscape and applications of multi-omics in nsCL/P, and explored the potential opportunities and challenges for future clinical practice.