scholarly journals Incidental Prenatal Diagnosis of Sex Chromosome Aneuploidies: Health, Behavior, and Fertility

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
J. J. P. M. Pieters ◽  
A. J. A. Kooper ◽  
A. Geurts van Kessel ◽  
D. D. M. Braat ◽  
A. P. T. Smits
Keyword(s):  
Prenatal Diagnosis ◽  
Reproductive Health ◽  
Prognostic Value ◽  
Sex Chromosome ◽  
Prenatal Testing ◽  
Cochrane Library ◽  
Medical Subject Headings ◽  
The Cochrane Library ◽  
Chromosomal Aneuploidies ◽  
Sex Chromosome Aneuploidies

Objective. To assess the diagnostic relevance of incidental prenatal findings of sex chromosome aneuploidies. Methods. We searched with medical subject headings (MeSHs) and keywords in Medline and the Cochrane Library and systematically screened publications on postnatally diagnosed sex chromosomal aneuploidies from 2006 to 2011 as well as publications on incidentally prenatally diagnosed sex chromosomal aneuploidies from 1980 to 2011. Results. Postnatally diagnosed sex chromosomal aneuploidies demonstrated three clinical relevant domains of abnormality: physical (22–100%), behavior (0–56%), and reproductive health (47–100%), while incidentally prenatally diagnosed sex chromosomal aneuploidies demonstrated, respectively, 0–33%, 0–40%, and 0–36%. Conclusion. In the literature incidental prenatal diagnosis of sex chromosomal aneuploidies is associated with normal to mildly affected phenotypes. This contrasts sharply with those of postnatally diagnosed sex chromosomal aneuploidies and highlights the importance of this ascertainment bias towards the prognostic value of diagnosis of fetal sex chromosomal aneuploidies. This observation should be taken into account, especially when considering excluding the sex chromosomes in invasive prenatal testing using Rapid Aneuploidy Detection.

scholarly journals Maternal Mosaicism Is a Significant Contributor to Discordant Sex Chromosomal Aneuploidies Associated with Noninvasive Prenatal Testing

2014 ◽  
Vol 60 (1) ◽  
pp. 251-259 ◽  
Author(s):  
Yanlin Wang ◽  
Yan Chen ◽  
Feng Tian ◽  
Jianguang Zhang ◽  
Zhuo Song ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Massively Parallel Sequencing ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Noninvasive Prenatal Testing ◽  
The Common ◽  
Chromosomal Aneuploidies ◽  
Sex Chromosome Aneuploidies

Abstract BACKGROUND In the human fetus, sex chromosome aneuploidies (SCAs) are as prevalent as the common autosomal trisomies 21, 18, and 13. Currently, most noninvasive prenatal tests (NIPTs) offer screening only for chromosomes 21, 18, and 13, because the sensitivity and specificity are markedly higher than for the sex chromosomes. Limited studies suggest that the reduced accuracy associated with detecting SCAs is due to confined placental, placental, or true fetal mosaicism. We hypothesized that an altered maternal karyotype may also be an important contributor to discordant SCA NIPT results. METHODS We developed a rapid karyotyping method that uses massively parallel sequencing to measure the degree of chromosome mosaicism. The method was validated with DNA models mimicking XXX and XO mosaicism and then applied to maternal white blood cell (WBC) DNA from patients with discordant SCA NIPT results. RESULTS Sequencing karyotyping detected chromosome X (ChrX) mosaicism as low as 5%, allowing an accurate assignment of the maternal X karyotype. In a prospective NIPT study, we showed that 16 (8.6%) of 181 positive SCAs were due to an abnormal maternal ChrX karyotype that masked the true contribution of the fetal ChrX DNA fraction. CONCLUSIONS The accuracy of NIPT for ChrX and ChrY can be improved substantially by integrating the results of maternal-plasma sequencing with those for maternal-WBC sequencing. The relatively high frequency of maternal mosaicism warrants mandatory WBC testing in both shotgun sequencing– and single-nucleotide polymorphism–based clinical NIPT after the finding of a potential fetal SCA.

scholarly journals Noninvasive prenatal detection of fetal sex chromosome abnormalities using the semiconductor sequencing platform (SSP) in Southern China

2021 ◽  
Vol 38 (3) ◽  
pp. 727-734
Author(s):  
Jiexia Yang ◽  
Yaping Hou ◽  
Fangfang Guo ◽  
Haishan Peng ◽  
Dongmei Wang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Sex Chromosome ◽  
Southern China ◽  
Prenatal Testing ◽  
Clinical Genetic ◽  
Fetal Sex ◽  
Sequencing Platform ◽  
Cell Free Fetal Dna ◽  
Fetal Aneuploidies

Abstract Background Noninvasive prenatal testing (NIPT) has been widely used to screen for fetal aneuploidies, including fetal sex chromosome aneuploidies (SCAs). However, there is less information on the performance of NIPT in detecting SCAs. Methods A cohort of 47,800 pregnancies was recruited to review the high-risk NIPT results for SCAs. Cell-free fetal DNA (cffDNA) was extracted and sequenced. All NIPT high-risk cases were recommended to undergo invasive prenatal diagnosis for karyotyping analysis and chromosome microarray analysis (CMA). Results A total of 238 high-risk cases were detected by NIPT, including 137 cases of 45,X, 27 cases of 47,XXX, and 74 cases of 47,XYY/47,XXY. Prenatal diagnosis, including karyotyping analysis and CMA, was available in 170 cases. The positive predictive value (PPV) was 30.00% for 45,X, 70.58% for 47,XXX, and 81.13% for 47,XYY/47,XXY. In addition, 13 cases of sex chromosome mosaicism and 9 cases of sex chromosome CNVs were incidentally found in this study. Conclusion Our study showed that NIPT was reliable for screening SCAs based on a large sample, and it performed better in predicting sex chromosome trisomies than monosomy X. Our study will provide an important reference for clinical genetic counseling and further processing of the results.

Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies

2021 ◽  
pp. 1-9
Author(s):  
Yunfang Shi ◽  
Xiaozhou Li ◽  
Duan Ju ◽  
Yan Li ◽  
Xiuling Zhang ◽  
...  
Keyword(s):  
Screening Tool ◽  
Sex Chromosome ◽  
Diagnostic Testing ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Chromosome Abnormalities ◽  
Noninvasive Prenatal Testing ◽  
Sex Chromosome Abnormalities ◽  
Sex Chromosome Aneuploidies ◽  
Mosaic Karyotype

<b><i>Objective:</i></b> This study was designed to investigate the efficiency of noninvasive prenatal testing (NIPT) for screening fetal sex chromosome aneuploidies (SCAs) through sequencing of cell-free DNA in maternal plasma. <b><i>Methods:</i></b> This is a retrospective study on the positive NIPT results for SCAs collected from our hospital between January 2012 and December 2018. Samples with positive NIPT results for SCAs were then confirmed by prenatal or postnatal karyotyping analysis. <b><i>Results:</i></b> After cytogenetic analysis, abnormal karyotypes were confirmed in 104 cases and the overall positive predictive value (PPV) of NIPT for SCAs was 43.40% (102/235). The most frequently detected karyotypes included 47,XXY (<i>n</i> = 42), 47,XXX (<i>n</i> = 20), 47,XYY (<i>n</i> = 16), and 45,X (<i>n</i> = 2). Meanwhile, 10 cases were confirmed with mosaic karyotype 45,X/46,XX and 14 cases with numerical or structural chromosome abnormalities, including a double trisomy 48,XXX,+18. Cytogenetic results from the other 131 cases showed normal XX or XY, which were discordant with NIPT results. Upon analysis of parental karyotypes, 29 (12.34%) showed false positivity in NIPT results that were caused by maternal sex chromosome abnormalities. <b><i>Conclusion:</i></b> NIPT is an effective screening tool for SCA with a PPV of 43.40%. Maternal karyotype abnormalities occurred in 12.34% of the cases with abnormal NIPT. Diagnostic testing of the fetus and the mother are recommended.

scholarly journals Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 42,910 single pregnancies with different clinical features

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Yibo Chen ◽  
Qi Yu ◽  
Xiongying Mao ◽  
Wei Lei ◽  
Miaonan He ◽  
...  
Keyword(s):  
Clinical Features ◽  
Sex Chromosome ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Testing ◽  
Detection Rates ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
Sex Chromosome Aneuploidies

Abstract Background Since the discovery of cell-free DNA (cfDNA) in maternal plasma, it has opened up new approaches for non-invasive prenatal testing. With the development of whole-genome sequencing, small subchromosomal deletions and duplications could be found by NIPT. This study is to review the efficacy of NIPT as a screening test for aneuploidies and CNVs in 42,910 single pregnancies. Methods A total of 42,910 single pregnancies with different clinical features were recruited. The cell-free fetal DNA was directly sequenced. Each of the chromosome aneuploidies and the subchromosomal microdeletions/microduplications of PPV were analyzed. Results A total of 534 pregnancies (1.24%) were abnormal results detected by NIPT, and 403 pregnancies had underwent prenatal diagnosis. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), and other chromosome aneuploidy was 79.23%, 54.84%, 13.79%, 33.04%, and 9.38% respectively. The PPV for CNVs was 28.99%. The PPV for CNVs ≤ 5 Mb is 20.83%, for within 5–10 Mb 50.00%, for > 10 Mb 27.27% respectively. PPVs of NIPT according to pregnancies characteristics are also different. Conclusion Our data have potential significance in demonstrating the usefulness of NIPT profiling not only for common whole chromosome aneuploidies but also for CNVs. However, this newest method is still in its infancy for CNVs. There is still a need for clinical validation studies with accurate detection rates and false positive rates in clinical practice.

scholarly journals Parental willing to take invasive diagnosis after Expanded Noninvasive Prenatal Testing (expanded NIPT) in a cohort of 24768 cases

2020 ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Copy Number Variations ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Prenatal Test ◽  
Xyy Syndrome ◽  
Chromosomal Aneuploidies

Abstract BackgroundThe main aims of the study were to investigate the performance of expanded noninvasive prenatal test (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs) and copy number variations (CNVs) and parental willing to taking invasive prenatal diagnosis after expanded NIPT in China.ResultsOf the 24,736 cases, successful follow-up was conducted in 92.2% (411/446) cases. The sensitivity of expanded NIPT test was 98.61%,90.91% and 100% and specificity was 99.91%,99.95% and 99.87% for the detection of trisomies 21, 18 and 13 respectively. Expanded NIPT detected 45, XO, 47, XXX, 47, XXY, XYY syndrome, RATs and CNVs with positive predictive values of 57.39%, 19.61%, 75%, 79.41%, 77.78%, 10% and 56.25% respectively. The women carrying fetuses with T21/T18/T13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those positive for SCAs, RATs and CNVs.ConclusionsOur study demonstrates that the expanded NIPT detects fetal trisomies 21,18 and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs and CNVs is still relatively poor and needed to be improved. With a positive expanded NIPT result, the women at high risk for common trisomies are more willing to take invasive prenatal diagnosis and terminate their pregnancies.* the first two authors contribute equally to this study.

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