Keywords
Sex chromosome abnormalities
Karyotype analysis
Multiplex ligation probe amplification (MLPA)
Submitted : 2023-11-26
Accepted : 2023-12-11
Published : 2023-12-26
Abstract
Objective: To analyze the detection efficiency of non-invasive prenatal tests (NIPT) in single fetus sex chromosome abnormalities and explore the application value of NIPT in sex chromosome diseases. Method: A total of 47,770 singleton pregnant women received free NIPT at Dongguan Maternity and Infant Clinic. Pregnant women with NIPT results indicating sex chromosome abnormalities provided informed consent for amniocentesis and subsequent karyotype analysis and/or multiplex ligation probe amplification (MLPA) technology. The study also involved telephone follow-ups on test results and pregnancy outcomes, along with a retrospective analysis of the positive detection rate of sex chromosome abnormalities by NIPT. Results: Among the 47,770 pregnant women, NIPT identified sex chromosome abnormalities in 158 cases, resulting in a detection rate of 0.33%. Of these cases, 113 pregnant women opted for amniocentesis, while 36 declined. One newborn, whose parents refused puncture, was later diagnosed with cryptorchidism. 8 cases failed to follow up. Among the 113 cases undergoing amniocentesis, 55 were diagnosed with sex chromosome abnormalities. These included 7 cases of X monosomy, 24 cases of sex chromosome trisomy (14 cases of Klinefelter syndrome; 5 cases of Jacobs syndrome; 5 cases of trisomy X), and 24 cases with sex chromosome microdeletions and microduplications. Meanwhile, 58 cases had no abnormalities. The overall positive predictive value (PPV) of NIPT testing for sex chromosome abnormalities was 48.67%, with specific PPVs for monosomy X, Klinefelter syndrome, Jacobs syndrome, trisomy X, and sex chromosome microdeletions and microduplications being 6.19%, 12.39%, 4.42%, 4.42%, and 21.24% respectively. Conclusion: NIPT demonstrates high detection efficiency in sex chromosome diseases. However, the efficiency varies significantly across different chromosomal abnormalities. Pregnant women with NIPT results indicating sex chromosome abnormalities should undergo amniocentesis for karyotype analysis and MLPA.
References
Cao Z, 2010, Chinese Obstetrics and Gynecology. Clinical Edition. People’s Medical Publishing House, Beijing, 27–28.
Chen X, Zhu J, Hu J, et al., 2019, Research Progress in Non-Invasive Prenatal Genetic Testing Technology. Chinese Journal of Laboratory Medicine, 2019(6): 484–488.
Huang X, Sun L, 2022, Clinical Research on Non-Invasive Prenatal Testing in Screening for Fetal Sex Chromosome Diseases. Journal of Nanjing Medical University (Natural Science Edition), 42(7): 1018–1024 + 1035.
Zheng Y, Wan S, Dang Y, et al., 2019, Non-Invasive Prenatal Testing for Detection of Trisomy 13, 18, 21 and Sex Chromosome Aneuploidies in 8594 Cases. Ginekol Pol, 90(5): 270–273. https://doi.org/10.5603/GP.2019.0050
Margiotti K, Cesta A, Dello Russo C, et al., 2020, Cell-Free DNA Screening for Sex Chromosomal Aneuploidies in 9985 Pregnancies: Italian Single Experience. BMC Res Notes, 13(1): 167. https://doi.org/10.1186/s13104-020-05009-1
Shi W, Zhang H, Wu D, et al., 2017, Value of Cell Free Fetal DNA in Maternal Plasma to Fetal Aneuploidy Screening. Journal of Chinese Practical Diagnosis and Therapy, 31(9): 859–861. https://doi.org/10.13507/j.issn.1674-3474.2017.09.008
Chitty LS, 2021, Non-Invasive Prenatal Testing 10 Years On. Prenat Diagn, 41(10): 1187–1189. https://doi.org/10.1002/pd.6032
Lu X, 2021, Application of Non-Invasive Prenatal Testing Technology in Detecting Sex Chromosome Aneuploidy Diseases: A Retrospective Study of 45,773 Pregnant Women, thesis, Anhui Medical University.
Tang L, Liang A, Li Y, et al., 2020, Application Value of Non-Invasive Prenatal Detection Technique in Screening Abnormal Sex Chromosome Aneuploidy in Singleton Pregnant Women. Journal of Guangxi Medical University, 37(11): 2059–2062. https://doi.org/10.16190/j.cnki.45-1211/r.2020.11.021
Slater HR, Bruno DL, Ren H, et al., 2003, Rapid, High Throughput Prenatal Detection of Aneuploidy Using a Novel Quantitative Method (MLPA). J Med Genet, 40(12): 907–912. https://doi.org/10.1136/jmg.40.12.907
Qin Y, Li J, Ning S, 2018, Research and Application of Combined Multiplex Ligation-Dependent Probe Amplification (MLPA) and Chromosome Karyotype Analysis for the Prenatal Diagnosis of Fetal Chromosomes Aneuploid Abnormalities. Chinese Journal of Birth Health and Heredity, 26(3): 25–28. https://doi.org/10.13404/j.cnki.cjbhh.2018.03.009
Zhang Q, Hao S, Yan Y, et al., 2015, Analysis of Combined Prenatal Testing Results of 3812 Amniotic Fluid Cells for Rapid Diagnosis and Karyotype Analysis. China Maternal and Child Health Care, 30(35): 6281–6284.
Tang S, Mao Y, Chen X, et al., 2011, Application of Multiplex Ligation-Dependent Probe Amplification Technology for Rapid and High-Throughput Diagnosis of Fetal Chromosomal Aneuploidy Abnormalities. China Journal of Medical Genetics, 2011(2): 199–203.