Preliminary study on detection of fetal sex chromosomal aneuploidies by low-coverage sequencing of plasma cell-free DNA

  Background   Chromosome abnormality is an important factor leading to birth defects. The application of noninvasive prenatal test (NIPT) in clinical practice can not only detect the target diseases, but also the sex chromosome abnormalities, including numerical aberration, microdeletion and microduplication. However, there is a lack of evaluation in clinical detection efficiency.

  Objective   To explore the value of low-coverage sequencing technology in detecting sex chromosomal abnormalities of fetuses in clinical practice.

  Methods  From June 2018 to July 2021, 11 239 noninvasive prenatal test results were collected in the First Medical Center of Chinese PLA General Hospital. The age of pregnant women was from 17 to 46 years and the gestational week was from 12 to 31 weeks. Among them, 42 cases were confirmed with sex chromosomal abnormality by NIPT, and their prenatal testing results were analyzed.

  Results  Of the 11 239 NIPT screening results, 51 cases were reported as sex chromosome abnormality, with the positive rate of 0.45%. Forty-two cases underwent amniocentesis, and 22 cases of abnormal sex chromosomes were diagnosed, with the positive predictive value (PPV) of 52%. The results showed that 8 out of 18 reported as XO were confirmed (PPV: 44%), 12 out of 21 reported as trisomies (XXX, XXY, XYY) were confirmed (PPV: 57%), and 2 out of 3 reported as other sex chromosomal aneuploidies were confirmed (PPV: 67%).

  Conclusion  NIPT can be an option for fetal sex chromosome abnormality screening, and is capable of detecting rare sex chromosomal aneuploidy, microdeletion and microduplication. However, the overall false positive rate is high.