DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study

Palomaki, Glenn E.; Deciu, Cosmin; Kloza, Edward M.; Lambert-Messerlian, Geralyn; Haddow, James E.; Neveux, Louis M.; Ehrich, Mathias; Boom, Dirk van den; Bombard, Allan T.; Grody, Wayne W.; Nelson, Stanley F.; Canick, Jacob A.

doi:10.1038/gim.2011.73

Cited by 465 publications

(509 citation statements)

References 23 publications

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“…Another study then, demonstrated the ability of MPS of maternal plasma to detect fetal trisomy 21 with a near 99% sensitivity and specificity in high-risk pregnancies, defined by maternal age, family history or positive serum and/or sonographic screening tests [7]. The group then published an analysis from the same study demonstrating the detection of trisomy 18 (Edwards syndrome) at 100% sensitivity with a false-positive rate of 0.28%, and trisomy 13 (Patau syndrome) at 91.7% sensitivity with a false-positive rate of 0.97% [28]. The overall detection rate for trisomy 13, 18, and 21 was reported as 98.9% sensitivity with a false-positive rate of 1.4%.…”

Section: Cell-free Dnamentioning

confidence: 99%

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

Kotsopoulou¹,

Tsoplou²,

Mavrommatis

et al. 2015

Diagnosis

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With the discovery of existing circulating cellfree fetal DNA (ccffDNA) in maternal plasma and the advent of next-generation sequencing (NGS) technology, there is substantial hope that prenatal diagnosis will become a predominately non-invasive process in the future. At the moment, non-invasive prenatal testing (NIPT) is available for high-risk pregnancies with significant better sensitivity and specificity than the other existing non-invasive methods (biochemical and ultrasonographical). Mainly it is performed by NGS methods in a few commercial labs worldwide. However, it is expected that many other labs will offer analogous services in the future in this fastgrowing field with a multiplicity of in-house methods (e.g., epigenetic, etc.). Due to various limitations of the available methods and technologies that are explained in detail in this manuscript, NIPT has not become diagnostic yet and women may still need to undergo risky invasive procedures to verify a positive finding or to secure (or even expand) a negative one. Efforts have already started to make the NIPT technologies more accurate (even at the level of a complete fetal genome) and cheaper and thus more affordable, in order to become diagnostic screening tests for all pregnancies in the near future.

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Section: Cell-free Dnamentioning

confidence: 99%

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

Kotsopoulou¹,

Tsoplou²,

Mavrommatis

et al. 2015

Diagnosis

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“…4,[10][11][12] Others have demonstrated a detection rate of over 98% with a false positive rate of less than 0.5%. [13][14][15][16][17][18][19][20] Thus, non-invasive prenatal testing (NIPT) seems to be the most effective screening method in women at high risk 21 and is already available at private laboratories in Brazil for tracking autosomal and sexual aneuploidies.…”

Section: Introductionmentioning

confidence: 99%

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X

Goulart

Liao

Carvalho

et al. 2016

Rev. Assoc. Med. Bras.

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Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; p=0.005). No predictive factors were identified in the T13/18 group. Intra-uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

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“…[9][10][11][12][13][14] Using this technology, non-invasive prenatal diagnostic (NIPD) for trisomy 21, 18 and 13 has recently reached the clinical setting by analysing the relative amount of chromosomes in circulating cell-free DNA from maternal plasma. 15,16 However, approaches permitting reliable detection of single-gene mutations or single-nucleotide polymorphisms (SNPs) using cell-free fetal DNA in maternal plasma are still under development. This is considerably more difficult because it concerns fetal genetic changes that differ only slightly from the maternal genome.…”

Section: Introductionmentioning

confidence: 99%

Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to β-thalassaemia

et al. 2013

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b-Thalassaemia is one of the most common autosomal recessive single-gene disorder worldwide, with a carrier frequency of 12% in Cyprus. Prenatal tests for at risk pregnancies use invasive methods and development of a non-invasive prenatal diagnostic (NIPD) method is of paramount importance to prevent unnecessary risks inherent to invasive methods. Here, we describe such a method by assessing a modified version of next generation sequencing (NGS) using the Illumina platform, called 'targeted sequencing', based on the detection of paternally inherited fetal alleles in maternal plasma. We selected four single-nucleotide polymorphisms (SNPs) located in the b-globin locus with a high degree of heterozygosity in the Cypriot population. Spiked genomic samples were used to determine the specificity of the platform. We could detect the minor alleles in the expected ratio, showing the specificity of the platform. We then developed a multiplexed format for the selected SNPs and analysed ten maternal plasma samples from pregnancies at risk. The presence or absence of the paternal mutant allele was correctly determined in 27 out of 34 samples analysed. With haplotype analysis, NIPD was possible on eight out of ten families. This is the first study carried out for the NIPD of b-thalassaemia using targeted NGS and haplotype analysis. Preliminary results show that NGS is effective in detecting paternally inherited alleles in the maternal plasma.

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DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study

Cited by 465 publications

References 23 publications

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

Non-invasive prenatal testing (NIPT): limitations on the way to become diagnosis

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X

Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to β-thalassaemia

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