Cell-free DNA test for pathogenic copy number variations: A retrospective study.

Area of Science:

• Prenatal diagnostics
• Genetics
• Molecular biology

Background:

• Fetal ultrasound abnormalities can indicate underlying genetic conditions.
• Prenatal diagnosis of copy number variations (CNVs) is crucial for managing pregnancies.
• Cell-free DNA (cfDNA) testing is a non-invasive method for prenatal screening.

Purpose of the Study:

• To evaluate the detection rate (DR) of prenatal cell-free DNA testing for pathogenic CNVs (>2 Mb).
• To assess cfDNA test performance in pregnancies with identified fetal ultrasound abnormalities.

Main Methods:

• Retrospective study of 29 pregnant women with fetuses diagnosed with microdeletion/microduplication syndromes via CMA.
• Maternal plasma cfDNA was sequenced, with gains/losses >2 Mb reported.
• Quality control included >10M unique map reads per sample.

Main Results:

• The cfDNA test identified 24 CNVs in 21 fetuses with pathogenic CNVs confirmed by CMA.
• The overall DR for pathogenic CNVs >2 Mb was 69%.
• 22q11.2 microdeletions/microduplications showed high detection rates (80% and 75% respectively).

Conclusions:

• Prenatal cfDNA testing demonstrates a moderate DR for pathogenic CNVs (>2 Mb) in fetuses with ultrasound anomalies.
• cfDNA testing may serve as an early screening tool prior to ultrasound findings.
• Further clinical data and cost-effectiveness analyses are required.