Implementation of Exome Sequencing in Prenatal Diagnostics: Chances and Challenges

Area of Science:

• Medical Genetics
• Prenatal Diagnosis

Background:

• Whole exome sequencing (WES) is established in postnatal diagnostics.
• Implementation of WES in prenatal settings faces challenges like sample quality and interpretation consistency.

Purpose of the Study:

• To evaluate the utility of prenatal WES in a clinical setting.
• To assess the diagnostic yield and turnaround time of rapid WES for fetal anomalies.

Main Methods:

• Analysis of 28 fetus-parent trios using whole exome sequencing over one year.
• Focus on cases with unexplained ultrasound anomalies where chromosomal microarray was inconclusive.

Main Results:

• A diagnostic yield of 25% was achieved, identifying pathogenic or likely pathogenic variants.
• Detected mutations included autosomal recessive (4), de novo (2), and dominant (1) inheritance patterns.
• Average turnaround time was under 4 weeks.

Conclusions:

• Prenatal rapid WES offers timely decision-making for the current pregnancy.
• It facilitates genetic counseling for future pregnancies and extended family screening.
• Rapid WES shows potential as a valuable tool for investigating fetal anomalies when standard methods fail.