Trio exome sequencing is highly relevant in prenatal diagnostics

Area of Science:

• Medical Genetics
• Genomics
• Prenatal Diagnosis

Background:

• Approximately 3% of newborns exhibit malformations, with genetic factors contributing to 20% of these cases.
• High-throughput sequencing, particularly whole exome sequencing (WES), has revolutionized postnatal genetic diagnostics.
• Extending WES to prenatal diagnostics holds significant potential for identifying fetal genetic disorders.

Purpose of the Study:

• To evaluate the utility of trio exome sequencing (WES of fetus and parents) in prenatal diagnostics for pregnancies with fetal ultrasound abnormalities.
• To determine the diagnostic yield and identify specific genetic causes of abnormalities detected via WES in the prenatal setting.

Main Methods:

• Analysis of 500 pregnancies with fetal ultrasound abnormalities between July 2018 and October 2020.
• Inclusion of genetic counseling prior to WES testing of the fetus and parents (trio WES).

Main Results:

• Molecular genetic findings explained ultrasound abnormalities in 38% of affected fetuses.
• Disease-causing de novo variants were identified in 47% of cases with explained abnormalities.
• Pathogenic variants in autosomal recessive or X-linked genes were detected in 37% of cases, indicating recurrence risks.

Conclusions:

• Trio exome sequencing is a valuable tool for prenatal diagnostics, offering a high diagnostic yield and rapid turnaround time comparable to chromosomal analysis.
• WES effectively covers a broad range of genetic variations, aiding in the clarification of fetal abnormalities.
• Essential comprehensive interdisciplinary genetic counseling is crucial both before and after WES diagnostics.