Prenatal exome sequencing for the morphologically normal fetus: Should we be doing it?

Area of Science:

• Genetics
• Prenatal Diagnosis
• Medical Genomics

Background:

• Morphologically normal fetuses may carry undiagnosed genetic conditions.
• Prenatal diagnosis traditionally relies on ultrasound and invasive testing.
• Exome sequencing offers a comprehensive approach to genetic analysis.

Purpose of the Study:

• To evaluate the diagnostic yield of prenatal exome sequencing (pES) in fetuses with normal morphology.
• To determine the types and frequencies of genetic abnormalities detected by pES in this population.

Main Methods:

• Retrospective analysis of 254 families undergoing prenatal trio exome sequencing.
• Sequencing was performed on parental and fetal DNA samples.
• Data analyzed for diagnostic variants and carrier status.

Main Results:

• Abnormal findings were reported in 3.1% (8/254) of cases.
• Monogenic disorders were identified in 2.3% (6/254) of fetuses.
• Carrier status for recessive conditions was found in 0.8% (2/254) of couples.

Conclusions:

• Prenatal exome sequencing provides valuable genetic information for morphologically normal fetuses.
• pES requires robust genetic counseling protocols for pre-test and post-test management.
• This technology enhances prenatal genetic screening capabilities.