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International Journal of Molecular... Jun 2020Preimplantation genetic testing (PGT) is widely used today in in-vitro fertilization (IVF) centers over the world for selecting euploid embryos for transfer and to... (Review)
Review
BACKGROUND
Preimplantation genetic testing (PGT) is widely used today in in-vitro fertilization (IVF) centers over the world for selecting euploid embryos for transfer and to improve clinical outcomes in terms of embryo implantation, clinical pregnancy, and live birth rates.
METHODS
We report the current knowledge concerning these procedures and the results from different clinical indications in which PGT is commonly applied.
RESULTS
This paper illustrates different molecular techniques used for this purpose and the clinical significance of the different oocyte and embryo stage (polar bodies, cleavage embryo, and blastocyst) at which it is possible to perform sampling biopsies for PGT. Finally, genetic origin and clinical significance of embryo mosaicism are illustrated.
CONCLUSIONS
The preimplantation genetic testing is a valid technique to evaluated embryo euploidy and mosaicism before transfer.
Topics: Female; Fertilization in Vitro; Genetic Testing; Humans; Mosaicism; Ploidies; Pregnancy; Preimplantation Diagnosis
PubMed: 32575575
DOI: 10.3390/ijms21124381 -
Neurotherapeutics : the Journal of the... Apr 2020Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the... (Review)
Review
Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the highly variable inter-individual response to the therapies makes management of this condition often challenging. In the last two decades, a genetic etiology has been revealed in more than half of all epilepsies and single gene defects in ion channels or neurotransmitter receptors have been associated with most inherited forms of epilepsy, including some focal and lesional forms as well as specific epileptic developmental encephalopathies. Several genetic tests are now available, including targeted assays up to revolutionary tools that have made sequencing of all coding (whole exome) and non-coding (whole genome) regions of the human genome possible. These recent technological advances have also driven genetic discovery in epilepsy and increased our understanding of the molecular mechanisms of many epileptic disorders, eventually providing targets for precision medicine in some syndromes, such as Dravet syndrome, pyroxidine-dependent epilepsy, and glucose transporter 1 deficiency. However, these examples represent a relatively small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure control, and other clinical aspects, such as neurodevelopmental and neuropsychiatric comorbidities, have yet been possible to address. We herein summarize the most recent advances in genetic testing and provide up-to-date approaches for the choice of the correct test for some epileptic disorders and tailored treatments that are already applicable in some monogenic epilepsies. In the next years, the most probably scenario is that epilepsy treatment will be very different from the currently almost empirical approach, eventually with a "precision medicine" approach applicable on a large scale.
Topics: Epilepsy; Genetic Testing; Humans; Precision Medicine
PubMed: 31981099
DOI: 10.1007/s13311-020-00835-4 -
Nature Reviews. Genetics Jun 2013Genomic technologies are reaching the point of being able to detect genetic variation in patients at high accuracy and reduced cost, offering the promise of... (Review)
Review
Genomic technologies are reaching the point of being able to detect genetic variation in patients at high accuracy and reduced cost, offering the promise of fundamentally altering medicine. Still, although scientists and policy advisers grapple with how to interpret and how to handle the onslaught and ambiguity of genome-wide data, established and well-validated molecular technologies continue to have an important role, especially in regions of the world that have more limited access to next-generation sequencing capabilities. Here we review the range of methods currently available in a clinical setting as well as emerging approaches in clinical molecular diagnostics. In parallel, we outline implementation challenges that will be necessary to address to ensure the future of genetic medicine.
Topics: Animals; Evaluation Studies as Topic; Genetic Testing; Genome-Wide Association Study; Genomics; Humans; Karyotyping; Molecular Diagnostic Techniques; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; United States
PubMed: 23681062
DOI: 10.1038/nrg3493 -
Archives of Pathology & Laboratory... Nov 2017- Next-generation sequencing (NGS) is a technology being used by many laboratories to test for inherited disorders and tumor mutations. This technology is new for many... (Review)
Review
CONTEXT
- Next-generation sequencing (NGS) is a technology being used by many laboratories to test for inherited disorders and tumor mutations. This technology is new for many practicing pathologists, who may not be familiar with the uses, methodology, and limitations of NGS.
OBJECTIVE
- To familiarize pathologists with several aspects of NGS, including current and expanding uses; methodology including wet bench aspects, bioinformatics, and interpretation; validation and proficiency; limitations; and issues related to the integration of NGS data into patient care.
DATA SOURCES
- The review is based on peer-reviewed literature and personal experience using NGS in a clinical setting at a major academic center.
CONCLUSIONS
- The clinical applications of NGS will increase as the technology, bioinformatics, and resources evolve to address the limitations and improve quality of results. The challenge for clinical laboratories is to ensure testing is clinically relevant, cost-effective, and can be integrated into clinical care.
Topics: Computational Biology; DNA Mutational Analysis; Databases, Genetic; Genetic Diseases, Inborn; Genetic Testing; Health Care Costs; High-Throughput Nucleotide Sequencing; Humans; Laboratory Proficiency Testing; Mutation; Neoplasms; Systems Integration
PubMed: 28782984
DOI: 10.5858/arpa.2016-0501-RA -
Trends in Molecular Medicine Aug 2021Preimplantation genetic testing for aneuploidy (PGT-A) has become a routine add-on for in vitro fertilization (IVF) to determine whether human embryos are to be... (Review)
Review
Preimplantation genetic testing for aneuploidy (PGT-A) has become a routine add-on for in vitro fertilization (IVF) to determine whether human embryos are to be clinically utilized or disposed of. Studies claiming IVF outcome improvements following PGT-A, however, used highly selected patient populations or inappropriate statistical methodologies. PGT-A was never clinically validated in its ability to define a human embryo as chromosomal normal, mosaic, or aneuploid, nor certified by a regulatory body, or an authoritative professional organization. Because of a high false-positive rate, PGT-A, actually reduces live IVF birth chances for many patients. Furthermore, in recent studies the PGT-A hypothesis was demonstrated to be mistaken for biological, mathematical and technical reasons. PGT-A, therefore, should clinically only be offered within experimental study frameworks.
Topics: Aneuploidy; Cytogenetic Analysis; Female; Fertilization in Vitro; Genetic Testing; Humans; Mosaicism; Pregnancy; Pregnancy Outcome; Preimplantation Diagnosis; Prognosis; Reproductive Physiological Phenomena
PubMed: 33446425
DOI: 10.1016/j.molmed.2020.11.009 -
Handbook of Clinical Neurology 2018Many neurogenetic conditions are inherited and therefore diagnosis of a patient will have implications for the patient's relatives and can raise ethical issues.... (Review)
Review
Many neurogenetic conditions are inherited and therefore diagnosis of a patient will have implications for the patient's relatives and can raise ethical issues. Predictive genetic testing offers asymptomatic relatives the opportunity to determine their risk status for a neurogenetic condition, and professional guidelines emphasize patients' autonomy and informed, voluntary decision making. Beneficence and nonmaleficence both need to be considered when making decisions about disclosure and nondisclosure of genetic information and test results. There can be disclosure concerns and challenges in determining whose autonomy to prioritize when a patient makes a genetic testing decision that can reveal the genetic status of a relative (e.g., testing an adult child when the at-risk parent has not been tested). Ethical issues are prominent when genetic testing for neurogenetic conditions is requested prenatally, on minors, adoptees, adult children at 25% risk, and for individuals with psychiatric issues or cognitive impairment. Neurogenetic conditions can result in cognitive decline which can affect decisional capacity and lead to ethical challenges with decision making, informed consent, and determining the patient's ability to comprehend test results. The ethical implications of genetic testing and emerging issues, including direct-to-consumer genetic testing, disclosure of secondary findings from genomic sequencing, and use of apolipoprotein E testing in clinical and research settings, are also discussed. Resources for information about genetic testing practice guidelines, insurance laws, and directories of genetics clinics are included.
Topics: Central Nervous System Diseases; Cognition Disorders; Ethics, Medical; Genetic Counseling; Genetic Testing; Humans
PubMed: 29325614
DOI: 10.1016/B978-0-444-63233-3.00003-8 -
Genes Nov 2023Preimplantation genetic testing (PGT) has emerged as a revolutionary technique in the field of reproductive medicine, allowing for the selection and transfer of healthy... (Review)
Review
Preimplantation genetic testing (PGT) has emerged as a revolutionary technique in the field of reproductive medicine, allowing for the selection and transfer of healthy embryos, thus reducing the risk of transmitting genetic diseases. However, despite remarkable advancements, the implementation of PGT faces a series of limitations and challenges that require careful consideration. This review aims to foster a comprehensive reflection on the constraints of preimplantation genetic diagnosis, encouraging a broader discussion about its utility and implications. The objective is to inform and guide medical professionals, patients, and society overall in the conscious and responsible adoption of this innovative technology, taking into account its potential benefits and the ethical and practical challenges that it presents.
Topics: Pregnancy; Female; Humans; Genetic Testing; Preimplantation Diagnosis
PubMed: 38003038
DOI: 10.3390/genes14112095 -
Australian Journal of General Practice Mar 2019Genetic testing offers great benefit for the diagnosis of genetic conditions and to identify and manage risk for conditions such as familial breast cancer. However,...
BACKGROUND
Genetic testing offers great benefit for the diagnosis of genetic conditions and to identify and manage risk for conditions such as familial breast cancer. However, potential personal insurance implications exist for some patients who undergo genetic testing in Australia. Currently, insurance companies offering risk-rated products such as life insurance can use genetic test results to discriminate, which may adversely affect applicants' ability to secure a policy. Many comparable countries have banned or restricted life insurers' use of genetic results, while Australia still permits it. However, the industry proposes to introduce a moratorium limiting the use of genetic results for life insurance underwriting in mid-2019.
OBJECTIVE
This paper explores the implications of genetic testing for risk-rated insurance for the general practice workforce in Australia.
DISCUSSION
Advancements in technology and decreasing costs have resulted in rapid expansion in genetic/genomic testing, which is set to become part of mainstream healthcare. General practitioners (GPs) in Australia will have an increasingly significant part to play in the expanded use of this testing, and it is therefore important that GPs are aware of these issues.
Topics: Australia; Genetic Testing; Humans; Insurance Selection Bias; Insurance, Life; Truth Disclosure
PubMed: 31256467
DOI: 10.31128/AJGP-10-18-4722 -
Fertility and Sterility Feb 2021Recent advancements in reproductive genetics have resulted in the availability of an extraordinary amount of new and detailed information for patients and providers.... (Review)
Review
Recent advancements in reproductive genetics have resulted in the availability of an extraordinary amount of new and detailed information for patients and providers. Whereas this information can inform many who are facing difficult clinical decisions, it can also introduce complex and uncertain choices. Expanded carrier screening and preimplantation genetic diagnosis for aneuploidy are important examples of new genetic techniques that are now widely used in reproductive medicine. This paper will explore these techniques through a medical-legal prism to better understand the opportunities and obligations incumbent on both patients and providers in this new age of genetic diagnosis.
Topics: Female; Genetic Carrier Screening; Genetic Testing; Humans; Mosaicism; Pregnancy; Preimplantation Diagnosis; Reproductive Medicine
PubMed: 33579522
DOI: 10.1016/j.fertnstert.2020.11.027 -
Cold Spring Harbor Perspectives in... Nov 2020Humanism is a philosophy that emphasizes rational, scientific, and empiric analysis of the world we live in to improve the physical, social, and psychological life of... (Review)
Review
Humanism is a philosophy that emphasizes rational, scientific, and empiric analysis of the world we live in to improve the physical, social, and psychological life of humanity. Although individual genetic counselors may or may not identify as humanists, genetic counseling and genetic testing are primarily humanistic endeavors because they are situated in the context of humanistic medicine in the westernized world. Humanistic goals are also implicit and explicit in the profession and practice of genetic counselors. This review examines the relationship between humanism and genetic counseling, highlighting situations in which the two may be discordant, and suggests ways that genetic counselors can reconcile these discordances.
Topics: Genetic Counseling; Genetic Testing; Humanism; Humans
PubMed: 31548221
DOI: 10.1101/cshperspect.a036673