Prenatal Exome Sequencing: Background, Current Practice and Future Perspectives-A Systematic Review

Area of Science:

• Genetics
• Reproductive Medicine
• Genomic Medicine

Background:

• Next Generation Sequencing (NGS) has transformed prenatal diagnosis.
• Prenatal Exome Sequencing (pES) is increasingly used for fetuses with unexplained structural anomalies after normal chromosomal analysis.
• The diagnostic yield and interpretation of incidental, inconclusive, or negative findings in pES require further evaluation.

Purpose of the Study:

• To systematically review the diagnostic yield of pES in fetuses with structural anomalies.
• To assess the rates of inconclusive and negative results associated with pES.
• To analyze factors influencing pES efficiency.

Main Methods:

• Systematic literature review of studies on pES in prenatal diagnosis.
• Categorization of studies into two groups: general structural anomalies and specific anomaly classes.
• Data extraction on diagnostic yield, inconclusive findings, and negative results.

Main Results:

• The weighted average diagnostic yield for pES in fetuses with structural anomalies was 19%.
• The rate of inconclusive findings was 12% in the general structural anomalies group.
• Diagnostic yield varied significantly in specific anomaly classes, influenced by sample size and inclusion criteria.

Conclusions:

• Prenatal Exome Sequencing plays a crucial role in prenatal diagnosis for fetuses with structural anomalies.
• Standardization of access criteria and consensus on managing controversial findings are needed for widespread pES adoption.
• Further research should focus on optimizing pES efficiency and interpretation protocols.