RECENT DEVELOPMENTS IN NON-INVASIVE PRENATAL DIAGNOSIS AND TESTING

2014 ◽  
Vol 25 (3-4) ◽  
pp. 295-317 ◽  
Author(s):  
SUZANNE DRURY ◽  
MELISSA HILL ◽  
LYN S CHITTY
Keyword(s):  
Single Gene ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Non Invasive ◽  
Invasive Test ◽  
Single Gene Disorders ◽  
Cell Free Fetal Dna ◽  
Recent Developments ◽  
Next Generation Sequencing Ngs

The ability to obtain fetal material that could be used for prenatal genetic diagnosis without requirement for an invasive test was a watershed moment in antenatal care. Cell-free fetal DNA (cffDNA) was identified in the maternal plasma by Lo and colleagues in 19971and despite being technically challenging, non-invasive tests for fetal sex determination, fetal rhesus D (RHD) genotyping, some single gene disorders and the major aneuploidies are now being offered in clinical practice throughout the world2. Progress continues at pace and recent developments in next generation sequencing (NGS) are driving significant advances in research and in the clinical application of non-invasive prenatal testing (NIPT) and diagnosis (NIPD) (Table 1).

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

Diagnosis ◽  
2015 ◽  
Vol 2 (3) ◽  
pp. 141-158 ◽  
Author(s):  
Ioanna Kotsopoulou ◽  
Panagiota Tsoplou ◽  
Konstantinos Mavrommatis ◽  
Christos Kroupis
Keyword(s):  
Prenatal Testing ◽  
Maternal Plasma ◽  
Screening Tests ◽  
Positive Finding ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
The Future ◽  
The Moment ◽  
Next Generation Sequencing Ngs ◽  
Near Future

AbstractWith the discovery of existing circulating cell-free 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 fast-growing 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.

scholarly journals PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. A1-A11
Author(s):  
J Shaw ◽  
E Scotchman ◽  
N Chandler ◽  
L S Chitty
Keyword(s):  
Copy Number ◽  
Sex Chromosome ◽  
Single Gene ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Aneuploidy Screening ◽  
Preimplantation Genetic Testing ◽  
Non Invasive ◽  
Single Gene Disorders ◽  
Cell Free Fetal Dna

The discovery of cell-free fetal DNA (cffDNA) in maternal plasma has enabled a paradigm shift in prenatal testing, allowing for safer, earlier detection of genetic conditions of the fetus. Non-invasive prenatal testing (NIPT) for fetal aneuploidies has provided an alternative, highly efficient approach to first-trimester aneuploidy screening, and since its inception has been rapidly adopted worldwide. Due to the genome-wide nature of some NIPT protocols, the commercial sector has widened the scope of cell-free DNA (cfDNA) screening to include sex chromosome aneuploidies, rare autosomal trisomies and sub-microscopic copy-number variants. These developments may be marketed as ‘expanded NIPT’ or ‘NIPT Plus’ and bring with them a plethora of ethical and practical considerations. Concurrently, cfDNA tests for single-gene disorders, termed non-invasive prenatal diagnosis (NIPD), have been developed for an increasing array of conditions but are less widely available. Despite the fact that all these tests utilise the same biomarker, cfDNA, there is considerable variation in key parameters such as sensitivity, specificity and positive predictive value depending on what the test is for. The distinction between diagnostics and screening has become blurred, and there is a clear need for the education of physicians and patients regarding the technical capabilities and limitations of these different forms of testing. Furthermore, there is a requirement for consistent guidelines that apply across health sectors, both public and commercial, to ensure that tests are validated and robust and that careful and appropriate pre-test and post-test counselling is provided by professionals who understand the tests offered.

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 Recent advances in prenatal genetic screening and testing

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2591 ◽  
Author(s):  
Ignatia B. Van den Veyver
Keyword(s):  
New Technologies ◽  
Single Gene ◽  
Chorionic Villus ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chorionic Villus Sampling ◽  
Non Invasive ◽  
Single Gene Disorders ◽  
Whole Exome ◽  
Cell Free Fetal Dna

The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy.

scholarly journals Would I have Wanted to Know? A Qualitative Exploration of Women’s Attitudes, Beliefs and Concerns about Non-Invasive Prenatal Testing for de novo Genetic Conditions after having a Child with a de novo Genetic Disorder

OBM Genetics ◽  
2021 ◽  
Vol 05 (04) ◽  
pp. 1-1
Author(s):  
Sarah Long ◽  
◽  
Roanna Lobo ◽  
Peter O'Leary ◽  
Jan E. Dickinson ◽  
...  
Keyword(s):  
Personal Growth ◽  
De Novo ◽  
Genetic Disorder ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Phenomenological Approach ◽  
Population Screening ◽  
Chromosomal Disorders ◽  
Non Invasive

Non-invasive prenatal testing (NIPT) for a panel of 25 single gene disorders became available in Western Australia in 2020 and potentially may be able to test for panels of hundreds of disorders as is the case with reproductive carrier screening. How this information would be used by parents in a population screening model is unknown. We used a phenomenological approach to explore retrospectively whether mothers of children with single gene or chromosomal disorders would have wanted to know about their child’s genetic diagnosis prior to delivery. Themes were identified such as having a child with a de novo disorder and effect on pregnancy outcomes in hypothetical situations, impact on family function, the diagnostic journey and personal growth. These themes related to both the concept of expanded NIPT (ENIPT) and the situation of having a child with a de novo genetic disorder that could now hypothetically be detected through ENIPT. Opinions were divided about whether participants would have wanted to know about their affected child’s condition, indicating any expanded NIPT testing panels would need to be offered in the context of an appropriate comprehensive counselling program. How this would be provided on a population screening level and the role of genetic counselling needs further exploration.

scholarly journals Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1890
Author(s):  
Luigia De Falco ◽  
Carmelo Piscopo ◽  
Rossana D’Angelo ◽  
Eloisa Evangelista ◽  
Teresa Suero ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Exome Sequencing ◽  
Single Gene ◽  
Disorders Of Sex Development ◽  
Prenatal Testing ◽  
Primary Amenorrhea ◽  
Disease Genes ◽  
Non Invasive ◽  
Sex Development ◽  
Cell Free Fetal Dna

Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive virilization. The patient described in this paper represents a case of discrepancies between non-invasive prenatal testing (NIPT) and ultrasound based fetal sex determination detected during prenatal screening. Exome sequencing was performed on the cell free fetal DNA (cffDNA), amniotic fluid, and the parents. Libraries were generated according to the manufacturer’s protocols using TruSight One Kits (Illumina Inc., San Diego, CA, USA). Sequencing was carried out on NEXT Seq 500 (Illumina) to mean sequencing depth of at least 100×. A panel of sexual disease genes was used in order to search for a causative variant. The finding of a mutation (c.645 A>T, p.Glu215Asp) in HSD17B3 gene in amniotic fluid as well as in cffDNA and both parents supported the hypothesis of the HSD17B3 deficiency. In conclusion, we used clinical exome sequencing and non-invasive prenatal detection, providing a solution for NIPT of a single-gene disorder. Early genetic diagnoses are useful for patients and clinicians, contribute to clinical knowledge of DSD, and are invaluable for genetic counseling of couples contemplating future pregnancies.

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