Detection of maternal X chromosome abnormalities using single nucleotide polymorphism-based noninvasive prenatal...

Area of Science:

• Genetics
• Prenatal Diagnostics
• Maternal Health

Background:

• Maternal X chromosome abnormalities can lead to discrepancies in noninvasive prenatal screening (NIPS) results.
• These discrepancies may result in unnecessary invasive testing for the fetus.
• Early diagnosis of maternal X chromosome abnormalities is crucial for managing reproductive and health risks.

Purpose of the Study:

• To validate a single nucleotide polymorphism (SNP)-based NIPS for detecting maternal X chromosome abnormalities.
• To assess the accuracy of NIPS in identifying specific maternal X chromosome conditions.

Main Methods:

• Prospective study design involving two groups: suspected maternal X abnormality (Group A, n=106) and suspected fetal aneuploidy (Group B, n=107).
• Maternal DNA isolated from plasma-depleted cellular pellets for blinded chromosomal microarray analysis.
• Criteria for abnormality: ≥5 Mb in size and present in ≥20% of DNA.

Main Results:

• Maternal X chromosome abnormalities were suspected in 0.08% of NIPS tests.
• NIPS confirmed maternal X chromosome abnormalities in 94.3% of Group A cases.
• Turner syndrome (45,X) and 47,XXX were the most common confirmed maternal abnormalities, with high detection rates.

Conclusions:

• NIPS demonstrates a high positive predictive value (94.3%) for maternal X chromosome abnormalities.
• A 100% negative predictive value was observed when screening for fetal chromosome abnormalities, indicating no maternal abnormalities were detected.
• Early identification of maternal X abnormalities via NIPS facilitates timely intervention for potential health complications.