The evolution of prenatal Whole Exome Sequencing: from cytogenetics to precision medicine
Abstract
Prenatal genetic diagnostics have undergone a remarkable transformation, progressing from early cytogenetic techniques such as karyotyping and fluorescence in situ hybridization (FISH) to chromosomal microarray analysis (CMA) and, most recently, whole exome sequencing (WES). WES has emerged as a groundbreaking tool, allowing for identifying single-gene mutations, small insertions and deletions, and other pathogenic variants responsible for rare and complex diseases. Unlike conventional approaches, which primarily detect large chromosomal abnormalities, WES provides a high-resolution analysis of the fetal genome, significantly improving diagnostic accuracy and enabling early intervention. This review explores the historical evolution of prenatal genetic testing, highlighting key milestones from the introduction of cytogenetics in the 1960s to the integration of WES in clinical practice over the last decade. WES has proven instrumental in diagnosing monogenic disorders, uncovering the genetic basis of fetal anomalies, and investigating cases of stillbirth and recurrent pregnancy loss (RPL). However, despite its immense clinical utility, challenges such as the interpretation of variants of uncertain significance (VUS), ethical concerns surrounding incidental findings, and the financial burden associated with sequencing continue to impact its widespread adoption. Future directions in WES include its potential integration with non-invasive prenatal testing (NIPT), advancements in artificial intelligence (AI)-driven bioinformatics, and its role in precision medicine, offering more personalized and data-driven approaches to prenatal care. As technological innovations continue to enhance the speed, accuracy, and affordability of WES, its role as a cornerstone of modern prenatal diagnostics is expected to expand, shaping the future of fetal genetic screening and clinical decision-making.
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Prenatal Whole Exome Sequencing (WES), Genetic Diagnostics, Monogenic Diseases, Chromosomal Microarray Analysis (CMA), Non-Invasive Prenatal Testing (NIPT), Variants of Uncertain Significance (VUS), Artificial Intelligence (AI) in Genomics
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