Purpose of review: Advancements in technologies have revolutionized prenatal diagnosis. Chromosomal microarray analysis (CMA) became a proven method and was implemented to detect gains and losses of DNA and absence of heterozygosity across the genome. Next-generation sequencing technologies have brought opportunities and challenges to genetic testing. Exome sequencing detects single-nucleotide variants (SNVs) across the exome and its prenatal application is an emerging field. We reviewed the literature to define the role of CMA and exome sequencing in prenatal diagnosis.
Recent finding: The application of exome sequencing in genetic diagnosis shows increased diagnostic yield and could be potentially implemented for prenatal diagnosis of fetuses with one or more ultrasound structural abnormalities or suspected monogenetic conditions. Although CMA is a gold standard for copy number variant (CNV) detection, large clinical cohort studies emphasized integrated CNV and SNV analyses for precise molecular diagnosis. Recent studies also suggest low-pass genome sequencing-based CNV detection can identify genome-wide imbalances at higher resolutions.
Summary: Data suggest exome sequencing for SNVs and CMA for CNV detection are the most effective approach for prenatal genetic diagnosis. Emerging evidences show genome sequencing has the potential to replace CMA and even exome sequencing to become a comprehensive genetic test in the clinical diagnostic laboratory.
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