Prenatal Screening for 22q11.2 Deletion Using a Targeted Microarray-Based Cell-Free DNA Test.

Area of Science:

• Genetics
• Molecular Biology
• Prenatal Diagnostics

Background:

• 22q11.2 deletion syndrome is a common genetic disorder.
• Accurate prenatal screening for 22q11.2 deletion is crucial for clinical management.
• Cell-free DNA (cfDNA) testing offers a non-invasive approach to prenatal screening.

Purpose of the Study:

• To evaluate the performance of a targeted microarray-based cfDNA test for identifying pregnancies at increased risk of 22q11.2 deletion.
• To assess the analytical and clinical accuracy of the Harmony Prenatal Test® for this specific genetic condition.

Main Methods:

• The study involved 1,953 plasma samples, divided into analytical validation (1,736 samples) and clinical verification (217 samples).
• Analytical validation assessed sensitivity and specificity using samples with known deletion status.
• Clinical verification used prospectively collected samples from pregnancies undergoing diagnostic testing for fetal deletion status.

Main Results:

• Analytical sensitivity for deletions (1.96-3.25 Mb) was 75.4%.
• Analytical specificity in presumed unaffected samples was at least 99.5%.
• In the clinical cohort, 5 of 7 affected pregnancies showed a high probability of deletion, with no false positives in 210 unaffected samples.

Conclusions:

• Targeted microarray-based cfDNA testing can identify pregnancies at increased risk for 22q11.2 deletions as small as 3.0 Mb.
• The test maintains a low false positive rate, enhancing its clinical utility.
• This cfDNA approach provides a valuable tool for prenatal screening of 22q11.2 deletion.