Cell-free DNA screening for sex chromosomal aneuploidies in 9985 pregnancies: Italian single experience.

Margiotti, Katia; Cesta, Anthony; Russo, Claudio Dello; Cima, Antonella; Barone, Maria Antonietta Barone; Viola, Antonella; Sparacino, Davide; Mesoraca, Alvaro; Giorlandino, Caludio

doi:10.21203/rs.3.rs-24164/v1

Cited by 3 publications

(3 citation statements)

References 10 publications

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“…NIPT‐plus is based on deeper sequencing and higher level analyses than traditional NIPT, and through data analysis algorithms NIPT‐plus is expected to find genome‐wide copy‐number variations (CNVs) associated with MMS. Growing studies demonstrated NIPT‐plus was also available for detecting fetal SCAs and MMS (Sund et al, 2020; Wu et al, 2020; Zheng et al, 2020), including DiGeorge syndrome (DGS), Prader–Willi/Angleman syndrome (PWS), cri du chat (CDC), and 1p36 microdeletion (1p36 del) syndrome, whereas its validity is still controversial (Christiaens et al, 2021; Margiotti et al, 2020). In our laboratory, NIPT‐plus has been used to report 17 types of fetal chromosome aneuploidies including T21, T18, T13, and SCAs, 76 types of MMS of which the CNVs size >10 Mb and 7 types of recurrent microdeletion syndromes of which the CNVs size >3 Mb.…”

Section: Introductionmentioning

confidence: 99%

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen

Zhang

et al. 2022

American J of Med Genetics Pt A

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The aim of this study was to determine the predictive value of expanded noninvasive prenatal testing (NIPT‐plus) for fetal chromosome abnormalities in the second trimester (12–26 weeks). We conducted a retrospective cohort study of 39,580 pregnancies with NIPT‐plus. Screening positive cases were diagnosed with karyotyping and single‐nucleotide polymorphism array analysis (SNP array)/copy number variation sequencing (CNV‐seq) with follow‐up. The positive predictive values (PPVs) of trisomy 21, 18, and 13 (T21, T18, and T13), sex chromosome aneuploidies (SCAs), and microdeletion and microduplication syndromes (MMS) by NIPT‐plus were recorded. We assessed the predictive value of NIPT‐plus based on maternal age and conventional indications. Of 39,580 pregnancies with NIPT‐plus, 511 (1.3%) had prenatal screening positive results of fetal chromosome abnormality, of which 87.7% (448/511) had invasive prenatal diagnosis. NIPT‐plus performed better in predicting fetal SCAs and chromosome aneuploidies for pregnancies with advanced maternal age (AMA) than young maternal age (YMA). Besides, the PPVs of T21, T13, and chromosome aneuploidies showed an upward trend when comparison was based on maternal age in 5‐year subintervals. The termination rates of 45,X, 47,XXX, 47,XXY, and 47,XYY were 100% (11/11), 20.0% (3/15), 91.7% (22/24), and 7.1% (1/14) with postnatal follow‐up. Last but not least, the PPV for MMS is 41.7% (30/72), which may have a positive correlation between the size of CNVs. Pregnant women with screen‐positive results for common trisomies (T13, T18, and T21) were more willing to conduct invasive prenatal diagnosis compared to those with positive results for SCAs or MMS. However, the current study demonstrated SCAs and MMS had the lowest PPV. This highlights the importance of confirmatory prenatal diagnosis in those patients and the potential impact on genetic counseling and informative decision‐making.

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Section: Introductionmentioning

confidence: 99%

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen

Zhang

et al. 2022

American J of Med Genetics Pt A

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“…The PPV data for SCAs adds to the more limited and variable clinical performance information available for these conditions 22–25 . Sensitivity and specificity estimates for SCAs were not calculated due to limited genetic confirmation in screen‐negative pregnancies, and we caution against studies that report test performance data for SCAs based on normal newborn physical exams.…”

Section: Discussionmentioning

confidence: 99%

Performance of a cell‐free DNA prenatal screening test, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low‐risk cell‐free DNA screening

et al. 2023

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Objectives: To evaluate the performance of cell-free DNA (cfDNA) screening for common fetal aneuploidies, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low-risk cfDNA screening.Method: A single-center prenatal cfDNA screening test was employed to detect trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs).Test performance, choice of prenatal procedure, and cytogenetic results in pregnancies with low-risk cfDNA screening were reviewed.Results: CfDNA screening of 38,289 consecutive samples identified 720 (1.9%) pregnancies at increased risk for aneuploidy. Positive predictive values (PPVs) for high-risk singleton pregnancies were 98.5% (T21), 92.5% (T18) and 55.2% (T13).PPVs for SCAs ranged from 30.6% to 95.2%. Most women elected chorionic villus sampling for prenatal diagnosis of T21, T18 and T13; amniocentesis and/or postnatal testing were commonly chosen for SCAs. Cytogenetic tests from 616 screennegative pregnancies identified 64 cases (12.7%) with chromosome conditions not detected by cfDNA screening, including triploidy (n = 30) and pathogenic and likely pathogenic copy number variants (n = 34). A further 15 (0.04%) false-negative common aneuploidy results were identified.Conclusions: CfDNA screening was highly accurate for detecting fetal aneuploidy in this general-risk obstetric population. Fetal ultrasound and prenatal diagnostic testing were important in identifying chromosome conditions in pregnancies screened as low-risk. Key pointsWhat's already known about this topic? � Prenatal cell-free DNA (cfDNA) screening for common autosomal trisomies has high sensitivity and specificity. Fewer data are available for sex chromosome aneuploidies (SCAs), which show greater variability in screening performance.

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“…Currently, prenatal diagnosis is made using preferably cell-free foetal DNA instead of invasive amniocentesis [99][100][101]. Postnatally, JS is detected by karyotyping from the patient's blood [91].…”

Section: Jacobs Syndromementioning

confidence: 99%

Skeletal and dental abnormalities in patients with sex chromosome aberrations: a systematic case-based review

Gruszczyński¹,

Nijakowski²,

Wolska-Bułach³

et al. 2022

polp

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Sex chromosome aneuploidies (SCAs) are common chromosomal disorders characterised by an atypical number of sex chromosomes. Turner syndrome (TS), Klinefelter syndrome (KS), and Jacobs syndrome (JS) are associated with a wide spectrum of skeletal manifestations, including craniofacial and limb anomalies. This systematic review aimed to analyse the incidence of skeletal abnormalities in selected SCAs based on case reports. In this review, 55 articles were included from the MEDLINE/PubMed and Google Scholar databases, according to PRISMA guidelines. High-arched palate, skeletal class II, and cubitus valgus were most frequently demonstrated among TS patients. Patients with KS and JS most often presented micrognathia, hypertelorism, and flat nasal bridge in the craniofacial region. In contrast, radioulnar synostosis, clinodactyly, and pes planus could be observed in the limbs of KS patients. The presence of dysmorphic facial features and limb malformations may indicate SCAs, which are underdiagnosed in the general population due to a variety of phenotypes.

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Cell-free DNA screening for sex chromosomal aneuploidies in 9985 pregnancies: Italian single experience.

Cited by 3 publications

References 10 publications

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Performance of a cell‐free DNA prenatal screening test, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low‐risk cell‐free DNA screening

Skeletal and dental abnormalities in patients with sex chromosome aberrations: a systematic case-based review

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