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Cold Spring Harbor Molecular Case... Jun 2019In the current era of personalized medicine, the field of oncology is witnessing a paradigm shift in patient care that is driving a tighter integration of genomic...
In the current era of personalized medicine, the field of oncology is witnessing a paradigm shift in patient care that is driving a tighter integration of genomic analysis modalities in patient care decision. This is driven by the expanding category of targeted therapies that require a broader understanding of the mutational profile of patient samples to more precisely guided personalized treatment decisions. Next-generation sequencing (NGS) has proved to be of tremendous power in detecting and characterizing a broad spectrum of activating or loss-of-function mutations across many gene targets. This power of NGS also results in significant challenges related to technical expertise, bioinformatics, computing infrastructure, laboratory practices, and integration into clinical decision-making. These challenges are particularly relevant to smaller and mid-tier hospital networks that are faced with the need to modernize their clinical practices and offer their patients access to advanced genomic technologies to improve outcomes. Adoption of such personalized medicine relies on information about a patient's cancer genome and the identification of its variants. This is best achieved using NGS. However, there are challenges to the adoption of such a complex technology and workflow, especially in smaller hospital systems. This commentary summarizes key considerations and challenges related to implementation of NGS in a community hospital setting.
Topics: Computational Biology; Genomics; High-Throughput Nucleotide Sequencing; Hospitals, Community; Humans; Medical Oncology; Mutation; Neoplasms; Precision Medicine; Sequence Analysis, DNA
PubMed: 31160354
DOI: 10.1101/mcs.a003707 -
Annals of Oncology : Official Journal... Aug 2019Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined...
ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach.
BACKGROUND
Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy.
METHODS
To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression.
RESULTS
The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types.
CONCLUSIONS
This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Biomarkers, Tumor; DNA Mismatch Repair; DNA Mutational Analysis; European Union; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Medical Oncology; Microsatellite Instability; Mutation; Neoplasms; Patient Selection; Practice Guidelines as Topic; Programmed Cell Death 1 Receptor; Societies, Medical
PubMed: 31056702
DOI: 10.1093/annonc/mdz116 -
Human Reproduction (Oxford, England) May 2019Which genes are confidently linked to human monogenic male infertility?
STUDY QUESTION
Which genes are confidently linked to human monogenic male infertility?
SUMMARY ANSWER
Our systematic literature search and clinical validity assessment reveals that a total of 78 genes are currently confidently linked to 92 human male infertility phenotypes.
WHAT IS KNOWN ALREADY
The discovery of novel male infertility genes is rapidly accelerating with the availability of next-generating sequencing methods, but the quality of evidence for gene-disease relationships varies greatly. In order to improve genetic research, diagnostics and counseling, there is a need for an evidence-based overview of the currently known genes.
STUDY DESIGN, SIZE, DURATION
We performed a systematic literature search and evidence assessment for all publications in Pubmed until December 2018 covering genetic causes of male infertility and/or defective male genitourinary development.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Two independent reviewers conducted the literature search and included papers on the monogenic causes of human male infertility and excluded papers on genetic association or risk factors, karyotype anomalies and/or copy number variations affecting multiple genes. Next, the quality and the extent of all evidence supporting selected genes was weighed by a standardized scoring method and used to determine the clinical validity of each gene-disease relationship as expressed by the following six categories: no evidence, limited, moderate, strong, definitive or unable to classify.
MAIN RESULTS AND THE ROLE OF CHANCE
From a total of 23 526 records, we included 1337 publications about monogenic causes of male infertility leading to a list of 521 gene-disease relationships. The clinical validity of these gene-disease relationships varied widely and ranged from definitive (n = 38) to strong (n = 22), moderate (n = 32), limited (n = 93) or no evidence (n = 160). A total of 176 gene-disease relationships could not be classified because our scoring method was not suitable.
LARGE SCALE DATA
Not applicable.
LIMITATIONS, REASONS FOR CAUTION
Our literature search was limited to Pubmed.
WIDER IMPLICATIONS OF THE FINDINGS
The comprehensive overview will aid researchers and clinicians in the field to establish gene lists for diagnostic screening using validated gene-disease criteria and help to identify gaps in our knowledge of male infertility. For future studies, the authors discuss the relevant and important international guidelines regarding research related to gene discovery and provide specific recommendations for the field of male infertility.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by a VICI grant from The Netherlands Organization for Scientific Research (918-15-667 to J.A.V.), the Royal Society, and Wolfson Foundation (WM160091 to J.A.V.) as well as an investigator award in science from the Wellcome Trust (209451 to J.A.V.).
PROSPERO REGISTRATION NUMBER
None.
Topics: Biomarkers; DNA Copy Number Variations; DNA Mutational Analysis; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Infertility, Male; Male; Reproducibility of Results; Exome Sequencing
PubMed: 30865283
DOI: 10.1093/humrep/dez022 -
BMC Medicine Feb 2019High-throughput non-invasive prenatal testing (NIPT) for fetal Rhesus D (RhD) status could avoid unnecessary treatment with anti-D immunoglobulin for RhD-negative women... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-throughput non-invasive prenatal testing (NIPT) for fetal Rhesus D (RhD) status could avoid unnecessary treatment with anti-D immunoglobulin for RhD-negative women found to be carrying an RhD-negative fetus. We aimed to assess the diagnostic accuracy of high-throughput NIPT for fetal RhD status in RhD-negative women not known to be sensitized to the RhD antigen, by performing a systematic review and meta-analysis.
METHODS
Prospective cohort studies of high-throughput NIPT used to determine fetal RhD status were included. The eligible population were pregnant women who were RhD negative and not known to be sensitized to RhD antigen. The index test was high-throughput, NIPT cell-free fetal DNA tests of maternal plasma used to determine fetal RhD status. The reference standard considered was serologic cord blood testing at birth. Databases including MEDLINE, EMBASE, and Science Citation Index were searched up to February 2016. Two reviewers independently screened titles and abstracts and assessed full texts identified as potentially relevant. Risk of bias was assessed using QUADAS-2. The bivariate and hierarchical summary receiver-operating characteristic (HSROC) models were fitted to calculate summary estimates of sensitivity, specificity, false positive and false negative rates, and the associated 95% confidence intervals (CIs).
RESULTS
A total of 3921 references records were identified through electronic searches. Eight studies were included in the systematic review. Six studies were judged to be at low risk of bias. The HSROC models demonstrated high diagnostic performance of high-throughput NIPT testing for women tested at or after 11 weeks gestation. In the primary analysis for diagnostic accuracy, women with an inconclusive test result were treated as having tested positive. The false negative rate (incorrectly classed as RhD negative) was 0.34% (95% CI 0.15 to 0.76) and the false positive rate (incorrectly classed as RhD positive) was 3.86% (95% CI 2.54 to 5.82). There was limited evidence for non-white women and multiple pregnancies.
CONCLUSIONS
High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin. The applicability of these findings to non-white women and women with multiple pregnancies is uncertain.
Topics: Female; Fetus; High-Throughput Nucleotide Sequencing; Humans; Pregnancy; Prenatal Care; Prenatal Diagnosis; Prospective Studies; Rh-Hr Blood-Group System
PubMed: 30760268
DOI: 10.1186/s12916-019-1254-4 -
Translational Psychiatry Feb 2019There has been a limited number of systematic reviews conducted to summarize the overview of the relationship between DNA methylation and depression, and to critically...
There has been a limited number of systematic reviews conducted to summarize the overview of the relationship between DNA methylation and depression, and to critically appraise the roles of major study characteristics in the accuracy of study findings. This systematic review aims to critically appraise the impact of study characteristics on the association between DNA methylation and depression, and summarize the overview of this association. Electronic databases and gray literatures until December 2017 were searched for English-language studies with standard diagnostic criteria of depression. A total of 67 studies were included in this review along with a summary of their study characteristics. We grouped the findings into etiological and treatment studies. Majority of these selected studies were recently published and from developed countries. Whole blood samples were the most studied common tissues. Bisulfite conversion, along with pyrosequencing, was widely used to test the DNA methylation level across all the studies. High heterogeneity existed among the studies in terms of experimental and statistical methodologies and study designs. As recommended by the Cochrane guideline, a systematic review without meta-analysis should be undertaken. This review has, in general, found that DNA methylation modifications were associated with depression. Subgroup analyses showed that most studies found BDNF and SLC6A4 hypermethylations to be associated with MDD or depression in general. In contrast, studies on NR3C1, OXTR, and other genes, which were tested by only few studies, reported mixed findings. More longitudinal studies using standardized experimental and laboratory methodologies are needed in future studies to enable more systematical comparisons and quantitative synthesis.
Topics: DNA Methylation; Depression; Depressive Disorder; Humans
PubMed: 30718449
DOI: 10.1038/s41398-019-0412-y -
BMC Cancer Jun 2018Invasive cervical cancer (ICC) is caused by high-risk human papillomavirus types (HR-HPVs) and is usually preceded by a long phase of intraepithelial neoplasia (CIN)....
BACKGROUND
Invasive cervical cancer (ICC) is caused by high-risk human papillomavirus types (HR-HPVs) and is usually preceded by a long phase of intraepithelial neoplasia (CIN). Before invasion, (epi) genetic changes, potentially applicable as molecular markers within cervical screening, occur in HPV host cells. Epigenetic alterations, such as dysregulation of microRNA (miRNA) expression, are frequently observed in ICC. The mechanisms and role of miRNA dysregulation in cervical carcinogenesis are still largely unknown.
METHODS
We provide an overview of the studies investigating miRNA expression in relation to ICC progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched through Pubmed database all articles between January 2010 and December 2017.
RESULTS
From the 24 studies retrieved, miR-29a and miR-21 are the most frequently down- and up-regulated in ICC progression, respectively. Microarray-based studies show a small overlap, with miR-10a, miR-20b, miR-9, miR-16 and miR-106 found repeatedly dysregulated. miR-34a, miR-125 and miR-375 were also found dysregulated in cervical exfoliated cells in relation to cancer progression.
CONCLUSIONS
The pivotal role of miRNAs in ICC progression and initial development is becoming more and more relevant. Available studies are essentially based on convenience material, entailing possible selection bias, and frequently of small size: all these points still represent a limitation to a wide comprehension of miRNAs relevant for ICC. The targeted approach instead of a genome-wide investigation still precludes the identification of all the relevant miRNAs in the process. The implementation of deep sequencing on large scale population-based studies will help to discover and validate the relation between altered miRNA expression and CC progression for the identification of biomarkers. Optimally, once explored on a miRNome scale, small specific miRNA signatures maybe used in the context of screening.
Topics: Biomarkers; Disease Progression; Female; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; Humans; MicroRNAs; Papillomavirus Infections; Uterine Cervical Neoplasms
PubMed: 29945565
DOI: 10.1186/s12885-018-4590-4 -
Journal of Biomedical Science Jun 2018Next-generation sequencing (NGS) is a powerful and high-throughput method for the detection of viral mutations. This article provides a brief overview about optimization... (Review)
Review
BACKGROUND
Next-generation sequencing (NGS) is a powerful and high-throughput method for the detection of viral mutations. This article provides a brief overview about optimization of NGS analysis for hepatocellular carcinoma (HCC)-associated hepatitis B virus (HBV) mutations, and hepatocarcinogenesis of relevant mutations.
MAIN BODY
For the application of NGS analysis in the genome of HBV, four noteworthy steps were discovered in testing. First, a sample-specific reference sequence was the most effective mapping reference for NGS. Second, elongating the end of reference sequence improved mapping performance at the end of the genome. Third, resetting the origin of mapping reference sequence could probed deletion mutations and variants at a certain location with common mutations. Fourth, using a platform-specific cut-off value to distinguish authentic minority variants from technical artifacts was found to be highly effective. One hundred and sixty-seven HBV single nucleotide variants (SNVs) were found to be studied previously through a systematic literature review, and 12 SNVs were determined to be associated with HCC by meta-analysis. From comprehensive research using a HBV genome-wide NGS analysis, 60 NGS-defined HCC-associated SNVs with their pathogenic frequencies were identified, with 19 reported previously. All the 12 HCC-associated SNVs proved by meta-analysis were confirmed by NGS analysis, except for C1766T and T1768A which were mainly expressed in genotypes A and D, but including the subgroup analysis of A1762T. In the 41 novel NGS-defined HCC-associated SNVs, 31.7% (13/41) had cut-off values of SNV frequency lower than 20%. This showed that NGS could be used to detect HCC-associated SNVs with low SNV frequency. Most SNV II (the minor strains in the majority of non-HCC patients) had either low (< 20%) or high (> 80%) SNV frequencies in HCC patients, a characteristic U-shaped distribution pattern. The cut-off values of SNV frequency for HCC-associated SNVs represent their pathogenic frequencies. The pathogenic frequencies of HCC-associated SNV II also showed a U-shaped distribution. Hepatocarcinogenesis induced by HBV mutated proteins through cellular pathways was reviewed.
CONCLUSION
NGS analysis is useful to discover novel HCC-associated HBV SNVs, especially those with low SNV frequency. The hepatocarcinogenetic mechanisms of novel HCC-associated HBV SNVs defined by NGS analysis deserve further investigation.
Topics: Carcinogenesis; Carcinoma, Hepatocellular; Hepatitis B virus; High-Throughput Nucleotide Sequencing; Humans; Liver Neoplasms; Mutation
PubMed: 29859540
DOI: 10.1186/s12929-018-0442-4 -
American Journal of Medical Genetics.... Jun 2018Holoprosencephaly (HPE) is a structural brain anomaly characterized by failure of the forebrain to separate during early embryogenesis. Both genetic and environmental... (Meta-Analysis)
Meta-Analysis
Holoprosencephaly (HPE) is a structural brain anomaly characterized by failure of the forebrain to separate during early embryogenesis. Both genetic and environmental etiologies of HPE have been discovered over the last three decades. Traditionally, the genetic workup for HPE has been a karyotype, chromosomal microarray, and/or Sanger sequencing of select genes. The recent increased availability of next-generation sequencing has changed the molecular diagnostic landscape for HPE, associating new genes with this disorder such as FGFR1. We conducted a systematic review of the medical literature for the molecular testing of HPE for studies published in the last 20 years. We also queried known commercial diagnostic laboratories and used information on their websites to construct a list of available commercial testing. Our group released its first recommendations in 2010 and this update incorporates the technology shifts and gene discoveries over the last decade. These recommendations provide a guide for genetic diagnosis of HPE, which is paramount for patients and their families for prognosis, treatment, and genetic counseling.
Topics: Algorithms; Alleles; Genes, Recessive; Genetic Counseling; Genetic Markers; Genetic Testing; High-Throughput Nucleotide Sequencing; Holoprosencephaly; Humans; Karyotyping
PubMed: 29771000
DOI: 10.1002/ajmg.c.31617 -
BMC Medical Genetics Feb 2018Kabuki syndrome (KS) is a rare pediatric congenital disorder with multiple congenital anomalies and intellectual disabilities, which is inherited in an autosomal...
BACKGROUND
Kabuki syndrome (KS) is a rare pediatric congenital disorder with multiple congenital anomalies and intellectual disabilities, which is inherited in an autosomal dominant manner. Mutations in KMT2D and KDM6A have been proven to be the primary cause in most cases of KS.
CASE PRESENTATION
Here we report two Chinese boys with clinical features of KS referred to our hospital for clinical diagnosis. Next-generation sequencing was performed on MiSeq to analyze the genetic mutations in both patients. In both, two novel de novo mutations in KMT2D gene (c.5235delA, p.(A1746Lfs*39) and c.7048G > A, p.(Q2350*)) were detected, both of which were subsequently confirmed by the two-generation pedigree analysis based on Sanger sequencing. A systematic literature review of previously reported mutational spectrum of KMT2D was also conducted.
CONCLUSIONS
Two novel de novo mutations in KMT2D gene were identified and considered to be pathogenic in both of KS patients. Our data adds information to the growing knowledge on the mutational spectrum of KS.
Topics: Abnormalities, Multiple; Amino Acid Sequence; Child, Preschool; DNA-Binding Proteins; Face; Hematologic Diseases; High-Throughput Nucleotide Sequencing; Histone Demethylases; Humans; Infant; Intellectual Disability; Male; Mutation; Neoplasm Proteins; Nuclear Proteins; Vestibular Diseases
PubMed: 29482518
DOI: 10.1186/s12881-018-0545-5 -
The Cochrane Database of Systematic... Nov 2017Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Triple X syndrome (47,XXX) and 47,XYY syndrome (47,XYY). Prenatal screening for fetal aneuploidies is standard care in many countries, but current biochemical and ultrasound tests have high false negative and false positive rates. The discovery of fetal circulating cell-free DNA (ccfDNA) in maternal blood offers the potential for genomics-based non-invasive prenatal testing (gNIPT) as a more accurate screening method. Two approaches used for gNIPT are massively parallel shotgun sequencing (MPSS) and targeted massively parallel sequencing (TMPS).
OBJECTIVES
To evaluate and compare the diagnostic accuracy of MPSS and TMPS for gNIPT as a first-tier test in unselected populations of pregnant women undergoing aneuploidy screening or as a second-tier test in pregnant women considered to be high risk after first-tier screening for common fetal aneuploidies. The gNIPT results were confirmed by a reference standard such as fetal karyotype or neonatal clinical examination.
SEARCH METHODS
We searched 13 databases (including MEDLINE, Embase and Web of Science) from 1 January 2007 to 12 July 2016 without any language, search filter or publication type restrictions. We also screened reference lists of relevant full-text articles, websites of private prenatal diagnosis companies and conference abstracts.
SELECTION CRITERIA
Studies could include pregnant women of any age, ethnicity and gestational age with singleton or multifetal pregnancy. The women must have had a screening test for fetal aneuploidy by MPSS or TMPS and a reference standard such as fetal karyotype or medical records from birth.
DATA COLLECTION AND ANALYSIS
Two review authors independently carried out study selection, data extraction and quality assessment (using the QUADAS-2 tool). Where possible, hierarchical models or simpler alternatives were used for meta-analysis.
MAIN RESULTS
Sixty-five studies of 86,139 pregnant women (3141 aneuploids and 82,998 euploids) were included. No study was judged to be at low risk of bias across the four domains of the QUADAS-2 tool but applicability concerns were generally low. Of the 65 studies, 42 enrolled pregnant women at high risk, five recruited an unselected population and 18 recruited cohorts with a mix of prior risk of fetal aneuploidy. Among the 65 studies, 44 evaluated MPSS and 21 evaluated TMPS; of these, five studies also compared gNIPT with a traditional screening test (biochemical, ultrasound or both). Forty-six out of 65 studies (71%) reported gNIPT assay failure rate, which ranged between 0% and 25% for MPSS, and between 0.8% and 7.5% for TMPS.In the population of unselected pregnant women, MPSS was evaluated by only one study; the study assessed T21, T18 and T13. TMPS was assessed for T21 in four studies involving unselected cohorts; three of the studies also assessed T18 and 13. In pooled analyses (88 T21 cases, 22 T18 cases, eight T13 cases and 20,649 unaffected pregnancies (non T21, T18 and T13)), the clinical sensitivity (95% confidence interval (CI)) of TMPS was 99.2% (78.2% to 100%), 90.9% (70.0% to 97.7%) and 65.1% (9.16% to 97.2%) for T21, T18 and T13, respectively. The corresponding clinical specificity was above 99.9% for T21, T18 and T13.In high-risk populations, MPSS was assessed for T21, T18, T13 and 45,X in 30, 28, 20 and 12 studies, respectively. In pooled analyses (1048 T21 cases, 332 T18 cases, 128 T13 cases and 15,797 unaffected pregnancies), the clinical sensitivity (95% confidence interval (CI)) of MPSS was 99.7% (98.0% to 100%), 97.8% (92.5% to 99.4%), 95.8% (86.1% to 98.9%) and 91.7% (78.3% to 97.1%) for T21, T18, T13 and 45,X, respectively. The corresponding clinical specificities (95% CI) were 99.9% (99.8% to 100%), 99.9% (99.8% to 100%), 99.8% (99.8% to 99.9%) and 99.6% (98.9% to 99.8%). In this risk group, TMPS was assessed for T21, T18, T13 and 45,X in six, five, two and four studies. In pooled analyses (246 T21 cases, 112 T18 cases, 20 T13 cases and 4282 unaffected pregnancies), the clinical sensitivity (95% CI) of TMPS was 99.2% (96.8% to 99.8%), 98.2% (93.1% to 99.6%), 100% (83.9% to 100%) and 92.4% (84.1% to 96.5%) for T21, T18, T13 and 45,X respectively. The clinical specificities were above 100% for T21, T18 and T13 and 99.8% (98.3% to 100%) for 45,X. Indirect comparisons of MPSS and TMPS for T21, T18 and 45,X showed no statistical difference in clinical sensitivity, clinical specificity or both. Due to limited data, comparative meta-analysis of MPSS and TMPS was not possible for T13.We were unable to perform meta-analyses of gNIPT for 47,XXX, 47,XXY and 47,XYY because there were very few or no studies in one or more risk groups.
AUTHORS' CONCLUSIONS
These results show that MPSS and TMPS perform similarly in terms of clinical sensitivity and specificity for the detection of fetal T31, T18, T13 and sex chromosome aneuploidy (SCA). However, no study compared the two approaches head-to-head in the same cohort of patients. The accuracy of gNIPT as a prenatal screening test has been mainly evaluated as a second-tier screening test to identify pregnancies at very low risk of fetal aneuploidies (T21, T18 and T13), thus avoiding invasive procedures. Genomics-based non-invasive prenatal testing methods appear to be sensitive and highly specific for detection of fetal trisomies 21, 18 and 13 in high-risk populations. There is paucity of data on the accuracy of gNIPT as a first-tier aneuploidy screening test in a population of unselected pregnant women. With respect to the replacement of invasive tests, the performance of gNIPT observed in this review is not sufficient to replace current invasive diagnostic tests.We conclude that given the current data on the performance of gNIPT, invasive fetal karyotyping is still the required diagnostic approach to confirm the presence of a chromosomal abnormality prior to making irreversible decisions relative to the pregnancy outcome. However, most of the gNIPT studies were prone to bias, especially in terms of the selection of participants.
Topics: Aneuploidy; Cell-Free Nucleic Acids; Chromosome Disorders; Disorders of Sex Development; Female; Fetal Diseases; High-Throughput Nucleotide Sequencing; Humans; Pregnancy; Pregnancy, High-Risk; Prenatal Diagnosis
PubMed: 29125628
DOI: 10.1002/14651858.CD011767.pub2