Detection of Microdeletions by Non-Invasive Prenatal Testing

[摘要] Background: Non-invasive prenatal testing (NIPT) is currently offered for the detection of Trisomy 21, 13, 18 and sex chromosome aneuploidy. The test is unique because it reaches nearly diagnostic levels of accuracy, otherwise achieved only by invasive procedures like chorionic villus sampling or amniocentesis, but requires only a sample of maternal blood. The NIPT technology continues to advance and a greater variety of genomic alterations can be detected. This research study describes the detection of two different fetal microdeletions using NIPT, which includes whole genome next-generation sequencing, and targeted region capture and sequencing methods. Methods: Whole genome next-generation sequencing, and targeted region capture and sequencing methods, were used on samples of maternal plasma obtained from pregnancies with confirmed microdeletions. The DNA of these samples was compared to control DNA libraries to identify the fetal microdeletions. Results: We were able to identify statistically significant differences between samples to detect fetal microdeletions on chromosome 12p12.1-p11.22 from maternal plasma samples. Identification of a fetal microdeletion on 5p15.33 from maternal plasma samples was achieved, but highlighted the difficulties in detection, and future challenges for NIPT. Conclusion: Our research has demonstrated the ability to detect microdeletions by whole genome next-generation sequencing and targeted region capture and sequencing methods of NIPT. The findings indicate the ability of NIPT to detect a wide range of genomic alterations, which will impact prenatal care in the future if the technology improves. Development and expansion of NIPT has significant public health implications due to its high levels of accuracy as compared to current screening, and safety for the pregnancy as compared to current diagnostic testing options. NIPT could have major ethical implications, and could impact the role of prenatal genetic counselors and physicians.

[发布机构] the University of Pittsburgh