scholarly journals Current controversies in prenatal diagnosis 2: Cell-free DNA prenatal screening should be used to identify all chromosome abnormalities

2018 ◽  
Vol 38 (3) ◽  
pp. 160-165 ◽  
Author(s):  
Lyn S. Chitty ◽  
Louanne Hudgins ◽  
Mary E. Norton
Keyword(s):  
Prenatal Diagnosis ◽  
Prenatal Screening ◽  
Chromosome Abnormalities ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals False Negative Cell-Free DNA Screening Result in a Newborn with Trisomy 13

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Yang Cao ◽  
Nicole L. Hoppman ◽  
Sarah E. Kerr ◽  
Christopher A. Sattler ◽  
Kristi S. Borowski ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
False Negative ◽  
Chromosome Abnormalities ◽  
Trisomy 13 ◽  
Cell Free Dna ◽  
Free Dna ◽  
Negative Cell ◽  
Cell Free Fetal Dna ◽  
Cfdna Screening ◽  
Screening Result

Background.Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy.Results.We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism.Conclusions.Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.

scholarly journals Non-Invasive Prenatal Diagnosis (NIPD) of Sickle-Cell Disease By Massively Parallel Sequencing of Cell-Free Fetal DNA in Maternal Serum

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2085-2085
Author(s):  
Yvonne Daniel ◽  
Julia Van Campen ◽  
Lee Silcock ◽  
Michael Yau ◽  
Joo Wook Ahn ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Massively Parallel Sequencing ◽  
Plasma Samples ◽  
Cell Disease ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Cell Free Fetal Dna

Sickle cell disease (SCD) is the most common genetic haematological disorder worldwide. Around 300.000 affected infants are born every year, including at least 1000 in the United States. Prenatal diagnosis is currently carried out using amniotic fluid or chorionic villus sampling. These invasive procedures are perceived to have a small risk of miscarriage. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived miscarriage risk. NIPD may also be more readily implemented than invasive prenatal diagnosis in the low-resource countries in which SCD is the most prevalent. However, accurate NIPD of autosomal recessive disorders such as sickle cell disease has proven challenging as this requires detection of fetal inheritance of a maternal allele from a mixed maternal-fetal pool of cell-free DNA. We report the development of a targeted massively parallel sequencing assay for the NIPD of fetal SCD using cell-free fetal DNA from maternal plasma. No paternal or previous offspring samples were required. 44 clinical samples were analysed, including 37 plasma samples from pregnant SCD carriers and 7 plasma samples from women with SCD due to Hb SC. We used a relative mutation dosage based approach for the 37 samples from maternal SCD carriers (Hb AS or Hb AC), integrating Unique Molecular Identifiers (UMIs) into the analysis to improve the accuracy of wildtype and mutant allele counts. We used a separate wildtype allele detection approach for the 7 samples from women with compound heterozygous SCD, in whom the detection of wildtype cell-free DNA indicates the presence of a carrier fetus. The success of the assay was evaluated by comparing results with the established fetal sickle status as determined through either invasive prenatal diagnosis or newborn screening. During development, two key factors improved the accuracy of the results: i) Selective analysis of only smaller cell-free DNA fragments enhanced the fetal fraction for all samples, with greater effects observed in samples from earlier gestations. This approach improved diagnostic accuracy: for 3 out of 44 samples, the genotype was inconclusive or incorrect before size selection, but correct after size selection. ii) Modifications to DNA fragment hybridisation capture optimised the diversity of Unique Molecular Identifier-tagged molecules analysed. This led to improvements in the results obtained for 5 samples, with 3 previously inconclusive samples correctly called and 2 previously discrepant results moved into the inconclusive range. In total, 37 results were concordant with the established fetal sickle status; this included 30/37 samples from carrier women and 7/7 samples from women with sickle cell disease due to Hb SC. The remaining 7 carrier samples gave an inconclusive result, which for 3 samples was attributed to a low fetal fraction. Samples from as early as 8 weeks gestation were successfully genotyped. There were no false positive or false negative results. This study is the largest to use NGS-based NIPD on clinical plasma samples from pregnancies at risk of SCD. Efforts to validate the assay on a larger sample cohort and to reduce the inconclusive rate are warranted. This study shows that NIPD for SCD is approaching clinical utility and has the potential to provide increased choice to women with pregnancies at risk of sickle cell disease. Disclosures Silcock: Nonacus Ltd.: Employment.

scholarly journals Isochromosome 21q is overrepresented among false-negative cell-free DNA prenatal screening results involving Down syndrome

2018 ◽  
Vol 26 (10) ◽  
pp. 1490-1496 ◽  
Author(s):  
Karin Huijsdens-van Amsterdam ◽  
Lieve Page-Christiaens ◽  
Nicola Flowers ◽  
Michael D Bonifacio ◽  
Katie M Battese Ellis ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Prenatal Screening ◽  
False Negative ◽  
Cell Free Dna ◽  
Free Dna ◽  
Negative Cell

Prenatal Screening

2018 ◽  
Author(s):  
Amber Mathiesen ◽  
Kali Roy
Keyword(s):  
Test Performance ◽  
Predictive Value ◽  
Prenatal Screening ◽  
Maternal Serum ◽  
Dna Testing ◽  
Maternal Serum Screening ◽  
Cell Free Dna ◽  
Free Dna ◽  
Serum Screening

This chapter provides information about a genetic counselor’s role in prenatal screening, including discussing and offering options to a patient, interpreting and providing results, or managing referrals based on abnormal results. It discusses how a screen is evaluated using sensitivity, specificity, positive predictive value, negative predictive value, and personal utility. It provides a detailed description of both maternal serum screening and cell-free DNA testing. The maternal serum screening discussion includes information on multiples of median, calculating risk, timing, pattern association, limitations, and follow-up. The review of cell-free DNA testing includes fetal fraction, methodology, test performance, limitations and considerations for testing, and follow-up. This chapter also provides a list of additional resources to use for cell-free DNA testing.

Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis

Transfusion ◽  
2001 ◽  
Vol 41 (12) ◽  
pp. 1524-1530 ◽  
Author(s):  
Hiromichi Ariga ◽  
Hitoshi Ohto ◽  
Michael P. Busch ◽  
Shinya Imamura ◽  
Robert Watson ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Maternal Circulation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Noninvasive Prenatal Diagnosis ◽  
Kinetics Of

scholarly journals At Preeclampsia Diagnosis, Total Cell‐Free DNA Concentration is Elevated and Correlates With Disease Severity

2021 ◽  
Author(s):  
Teodora R. Kolarova ◽  
Hilary S. Gammill ◽  
J. Lee Nelson ◽  
Christina M. Lockwood ◽  
Raj Shree
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Disease Severity ◽  
Gestational Age ◽  
Prenatal Screening ◽  
Tissue Injury ◽  
Screening Assay ◽  
Cell Free Dna ◽  
Free Dna ◽  
Gestational Age At Delivery

Background Placental derived cell‐free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA parameters are altered in preeclampsia, we conducted a case‐control study using prospectively collected maternal plasma (n=20 preeclampsia, n=22 normal) using our in‐house validated prenatal screening assay. Methods and Results Isolated cfDNA was quantified, sequenced using Illumina NextSeq 500, and the placental‐derived fraction was determined. Clinical and test characteristics were compared between preeclampsia and controls, followed by comparisons within the preeclampsia cohort dichotomized by cfDNA concentration. Lastly, cfDNA parameters in preeclampsia were correlated with markers of disease severity. Maternal age, body mass index, gestational age at delivery, cesarean rate, and neonatal birthweight were expectedly different between groups ( P ≤0.05). The placental‐derived cfDNA fraction did not differ between groups (21.4% versus 16.9%, P =0.06); however, total cfDNA was more than 10 times higher in preeclampsia (1235 versus 106.5 pg/µL, P <0.001). This relationship persisted when controlling for important confounders (OR 1.22, 95% CI 1.04–1.43, P =0.01). The dichotomized preeclampsia group with the highest cfDNA concentration delivered earlier (33.2 versus 36.6 weeks, P =0.02) and had lower placental‐derived fractions (9.1% versus 21.4%, P =0.04). Among preeclampsia cases, higher total cfDNA correlated with earlier gestational age at delivery ( P =0.01) and higher maximum systolic blood pressure ( P =0.04). Conclusions At diagnosis, total cfDNA is notably higher in preeclampsia, whereas the placental derived fraction remains similar to healthy pregnancies. In preeclampsia, higher total cfDNA correlates with earlier gestational age at delivery and higher systolic blood pressure. These findings may indicate increased release of cfDNA from maternal tissue injury.

scholarly journals When ultrasound anomalies are present: An estimation of the frequency of chromosome abnormalities not detected by cell-free DNA aneuploidy screens

2018 ◽  
Vol 38 (4) ◽  
pp. 250-257 ◽  
Author(s):  
Rebecca M. Reimers ◽  
Heather Mason-Suares ◽  
Sarah E. Little ◽  
Bryann Bromley ◽  
Emily S. Reiff ◽  
...  
Keyword(s):  
Chromosome Abnormalities ◽  
Cell Free Dna ◽  
Dna Aneuploidy ◽  
Free Dna

GENOME-WIDE PROFILING AND HAPLOTYPING OF CELL-FREE DNA ENABLING COMBINED NON-INVASIVE PRENATAL DIAGNOSIS OF INHERITED MONOGENIC DISEASES AND ANEUPLOIDY

2019 ◽  
Vol 39 ◽  
pp. e10-e11
Author(s):  
Huiwen Che ◽  
Darine Vileila ◽  
Eftychia Dimitriadou ◽  
Jia Ding ◽  
Thierry Voet ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Genome Wide ◽  
Monogenic Diseases
Sign in / Sign up

Export Citation Format

Share Document