Identification of copy number variants by NGS-based NIPT at low sequencing depth

Ye, Xiaoqing; Lin, Sheng Mou; Song, Xiwei; Tan, Meihua; Li, Jia; Wang, Jiayan; Yan, Huanchen; Zhang, Huimin; Li, Shaoying; Chen, Dunjin; Chen, Min

doi:10.1016/j.ejogrb.2020.11.026

Cited by 15 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When further copy number alterations are detectable by a NIPT platform, such as trisomies of other chromosomes, or specific microdeletion and microduplication syndromes (MDDs) (Weise et al, 2012), these protocols are marketed as "expanded NIPT" or "NIPT Plus" tests. For these emerging platforms, the data for Z-scores, sensitivity, specificity and PPVs are in most cases hard to find or are not provided (Skrzypek and Hui, 2017;Shaw et al, 2020;Ye et al, 2021).…”

Section: Nipt Is Not Equal To Niptmentioning

confidence: 99%

Non-invasive Prenatal Testing, What Patients Do Not Learn, May Be Due to Lack of Specialist Genetic Training by Gynecologists and Obstetricians?

Liehr

2021

Front. Genet.

View full text Add to dashboard Cite

Platforms for “non-invasive prenatal testing” (NIPT), or also referred to as “non-invasive prenatal screening” (NIPS) have been available for over 10 years, and are the most recent tools available to obtain information about genetic condition(s) of an unborn child. The highly praised advantage of NIPT-screening is that results can provide early hints on the detection of fetal trisomies and gonosomal numerical aberrations as early as the 10th week of gestation onward, without any need for invasive procedures, such as amniocenteses or alternatives. Understandably, the public along with gynecologists and obstetricians eagerly await these early test results. Their general hope for normal (=negative) test results is also justified, as in >95% of the tested cases such an outcome is to be expected. However, pregnant women can be disappointed and confused, particularly regarding the genetic information and proposed care when the results are positive, and these emotions are also common with false-positive and false-negative NIPT results. Finally, such concerns in understanding the advantages and limitations of this routinely ordered screening tool end up at Clinical Geneticists and Genetic counselors. In this review, general background on NIPT, differences of NIPT platforms, advantages and limitations of NIPT, as well as consequences of insufficient counseling before and after NIPT are summarized. To provide comprehensive care in all pregnancies situations, professionals need a careful attitude toward offering NIPT along with specially training and qualifications in counseling for these procedures. Often it is gynecologists and obstetricians who discuss the use of NIPT with patients; however, although these physicians have a highly qualified background and knowledge in their respective specialty area(s), they may lack specific training on the interpretation of NIPT-screening results. These potential knowledge gaps must be closed quickly and comprehensively by the corresponding scientific societies to ensure optimal patient care.

show abstract

Section: Nipt Is Not Equal To Niptmentioning

confidence: 99%

Non-invasive Prenatal Testing, What Patients Do Not Learn, May Be Due to Lack of Specialist Genetic Training by Gynecologists and Obstetricians?

Liehr

2021

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…The consistency rates of CNV location and size were 100% and 83.3%, respectively. The sensitivities differed markedly in other retrospective studies, ranging from 61.1 to 84.2% (Lefkowitz et al, 2016;Li et al, 2016;Liu et al, 2016;Cui et al, 2019;Hu et al, 2019;Hyblova et al, 2020;Ye et al, 2020). The DR differences may be attributed to the limited sample size in previous studies, as well as marked differences in CNV size and location.…”

Section: Discussionmentioning

confidence: 74%

“…Recent studies have shown that NIPS has good detection performance for fetal CNVs, especially for CNVs > 10 Mb (Liu et al, 2016;Yu et al, 2019). When the sequencing depth is increased, NIPS can also achieve satisfactory performance in detecting smaller CNVs, and the range of detectable CNV size can reach 2-7 Mb (Lefkowitz et al, 2016;Ye et al, 2020). However, the results presented here showed some discrepancies with previous studies, suggesting that in addition to the ability to detect CNVs was strongly dependent on the size of the CNVs, some specific CNVs are associated with the fetal fraction (Benn, 2016).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations

et al. 2021

View full text Add to dashboard Cite

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

show abstract

“…For instance, analysis of all 24 chromosomes (15)(16)(17)(18) and even detection of some monogenic conditions (19) are currently available in the portfolio of some laboratories offering cffDNA analysis worldwide. One of the most interesting advances in analysis of cffDNA in maternal blood is detection of placental copy number variations (CNVs) of a relatively long size without increasing sequencing depth (20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Inherited unbalanced reciprocal translocation with 3q duplication and 5p deletion in a foetus revealed by Cell-Free foetal DNA (cffDNA) testing: A case report

Ali¹,

Mateu‐Brull

Balaguer

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundSince 2011, screening maternal blood for cell-free foetal DNA (cffDNA) fragments has offered a robust clinical tool to classify pregnancy as low or high-risk for Down, Edwards, and Patau syndromes. With recent advances in molecular biology and improvements in data analysis algorithms, the screening’s scope of analysis continues to expand. Indeed, screening now encompassess additional conditions, including aneuploidies for sex chromosomes, microdeletions and microduplications, rare autosomal trisomies, and, more recently, segmental deletions and duplications called copy number variations (CNVs). Yet, the ability to detect CNVs creates a new challenge for cffDNA analysis in couples in which one member carries a structural rearrangement such as a translocation or inversion.Case presentationWe report a segmental duplication of the long arm of chromosome 3 and a segmental deletion of the short arm of chromosome 5 detected by cffDNA analysis in a 25-year-old pregnant woman. G-band karyotyping in amniotic fluid only detected an abnormality in chromosome 5. Next-generation sequencing in amniocytes confirmed both abnormalities and identified breakpoints in 3q26.32q29 and 5p13.3p15. The foetus died at 21 weeks of gestation due to multiple abnormalities, and later G-band karyotyping in the parents revealed that the father was a carrier of a balanced reciprocal translocation [46,XY,t(3;5)(q26.2;p13)]. Maternal karyotype appeared normal.ConclusionThis case provides evidence that extended cffDNA can detect, in addition to aneuploidies for whole chromosomes, large segmental aneuploidies. In some cases, this may indicate the presence of chromosomal rearrangements in a parent. Such abnormalities are outside the scope of standard cffDNA analysis targeting chromosomes 13, 18, 21, X, and Y, potentially leading to undiagnosed congenital conditions.

show abstract

Identification of copy number variants by NGS-based NIPT at low sequencing depth

Cited by 15 publications

References 28 publications

Non-invasive Prenatal Testing, What Patients Do Not Learn, May Be Due to Lack of Specialist Genetic Training by Gynecologists and Obstetricians?

Non-invasive Prenatal Testing, What Patients Do Not Learn, May Be Due to Lack of Specialist Genetic Training by Gynecologists and Obstetricians?

Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations

Inherited unbalanced reciprocal translocation with 3q duplication and 5p deletion in a foetus revealed by Cell-Free foetal DNA (cffDNA) testing: A case report

Contact Info

Product

Resources

About