Application of Non-Invasive Prenatal Testing for Dominant Single-Gene Disorders in an Intermediate-Risk Population: A...

Area of Science:

• Genetics
• Prenatal Diagnostics
• Molecular Biology

Background:

• Single-gene disorders (SGDs) pose a significant risk during pregnancy.
• Current screening methods for SGDs in intermediate-risk populations have limitations.
• Non-invasive prenatal testing (NIPT) has shown promise for various genetic analyses.

Purpose of the Study:

• To evaluate the feasibility and efficiency of NIPT for single-gene disorders (NIPT-SGD).
• To assess NIPT-SGD performance in a cohort of pregnant women at intermediate risk for dominant SGDs in China.

Main Methods:

• A prospective cohort study involving 2000 pregnant women at intermediate risk for SGDs.
• NIPT-SGD utilized a cell-free DNA (cfDNA) panel targeting 155 genes for 202 dominant SGDs.
• Genetic confirmation was performed via amniocentesis with Sanger sequencing or exome sequencing of newborn blood spots, followed by infant clinical follow-up.

Main Results:

• NIPT-SGD was analyzed in 1997 pregnancies, identifying 10 positive and 1987 negative cases.
• Diagnostic validation confirmed 7 true positives and 988 true negatives, with a sensitivity of 100% and specificity of 99.8%.
• Positive predictive value was 77.8%, and negative predictive value was 100%; 4 of 7 true-positive cases showed clinical correlation.

Conclusions:

• NIPT-SGD is a reliable and effective method for detecting fetal dominant SGDs in intermediate-risk pregnancies.
• Clinical implementation requires careful consideration due to potential ambiguities from variants in unaffected fetuses.