scholarly journals Issues and Challenges in Diagnostic Sequencing for Inherited Cardiac Conditions

2017 ◽  
Vol 63 (1) ◽  
pp. 116-128 ◽  
Author(s):  
Roddy Walsh ◽  
Stuart A Cook
Keyword(s):  
Genetic Testing ◽  
Clinical Management ◽  
Genomic Medicine ◽  
Predictive Testing ◽  
Underlying Disease ◽  
Inherited Disease ◽  
Cascade Screening ◽  
Clinical Genetic ◽  
Additional Information ◽  
Inherited Cardiac Conditions

Abstract BACKGROUND Inherited cardiac conditions are a relatively common group of Mendelian diseases associated with ill health and death, often in the young. Research into the genetic causes of these conditions has enabled confirmatory and predictive diagnostic sequencing to become an integral part of the clinical management of inherited cardiomyopathies, arrhythmias, aortopathies, and dyslipidemias. CONTENT Currently, the principle benefit of clinical genetic testing is the cascade screening of family members of patients with a pathogenic variant, enabling targeted follow up of presymptomatic genotype-positive individuals and discharge of genotype-negative individuals to health. For the affected proband, diagnostic sequencing can also be useful in discriminating inherited disease from alternative diagnoses, directing treatment, and for molecular autopsy in cases of sudden unexplained death. Advances in sequencing technology have expanded testing panels for inherited cardiac conditions and driven down costs, further improving the cost-effectiveness of genetic testing. However, this expanded testing requires great rigor in the identification of pathogenic variants, with domain-specific knowledge required for variant interpretation. SUMMARY Diagnostic sequencing has the potential to become an integral part of the clinical management of patients with inherited cardiac conditions. However, to move beyond just confirmatory and predictive testing, a much greater understanding is needed of the genetic basis of these conditions, the role of the environment, and the underlying disease mechanisms. With this additional information it is likely that genetic testing will increasingly be used for stratified and preventative strategies in the era of genomic medicine.

Current Approaches to Germline Cancer Genetic Testing

2020 ◽  
Vol 71 (1) ◽  
pp. 85-102
Author(s):  
Elena M. Stoffel ◽  
John M. Carethers
Keyword(s):  
Genetic Testing ◽  
Clinical Education ◽  
Genetic Predisposition ◽  
Genomic Medicine ◽  
Cancer Therapies ◽  
Clinical Genetic ◽  
Clinical Genetic Testing ◽  
Sequencing Technologies ◽  
Predisposition Genes ◽  
Generation Sequencing

The prevalence of genetic predisposition to cancer is greater than initially appreciated, yet most affected individuals remain undiagnosed. Deleterious germline variants in cancer predisposition genes are implicated in 1 in 10 cases of advanced cancer. Next-generation sequencing technologies have made germline and tumor DNA sequencing more accessible and less expensive. Expanded access to clinical genetic testing will improve identification of individuals with genetic predisposition to cancer and provide opportunities to effectively reduce morbidity through precision cancer therapies and surveillance. Cross-disciplinary clinical education in genomic medicine is needed to translate advances in genomic medicine into improved health outcomes.

scholarly journals Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients

2016 ◽  
Author(s):  
Angela George ◽  
Daniel Riddell ◽  
Sheila Seal ◽  
Sabrina Talukdar ◽  
Shazia Mahamdallie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Large Scale ◽  
Brca Mutation ◽  
Genomic Medicine ◽  
Cost Savings ◽  
Brca Testing ◽  
Clinical Genetic ◽  
Gene Testing

SUMMARYBackground:Advances in DNA sequencing have made gene testing fast and affordable, but adaptation of clinical services to capitalise on this for patient benefit has been slow. Ovarian cancer exemplifies limitations of current systems and potential benefits of increased gene testing. Approximately 15% of ovarian cancer patients have a germline mutation in BRCA1 or BRCA2 (collectively termed ‘BRCA’) and this has substantial implications for their personal management and that of their relatives. However, in most countries implementation of BRCA testing in ovarian cancer has been inconsistent and largely unsuccessful.Methods:We developed a mainstream pathway in which BRCA testing was undertaken by cancer team members after 30 minutes online training. Patients with a mutation were sent a genetic appointment with their results. Cascade testing to relatives was performed via standard clinical genetic procedures.Findings:207 women with ovarian cancer were offered gene testing through the mainstream pathway and all accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease including 97% (32/33) women with a mutation. All mutation-positive women and ~3.5 relatives per family have been seen in genetics. Patient and clinician feedback was very positive. >95% found the pathway to be simple and effective. The pathway offers considerable reduction in time (~5-fold) and resource requirements (~13-fold) compared to the traditional genetic pathway. We estimate it would deliver £2.6M NHS cost savings per year, and would allow implementation of national testing recommendations with existing infrastructure.Interpretation:Mainstream genetic testing is effective, efficient and patient-centred and offers a mechanism for large-scale implementation of BRCA gene testing in cancer patients. The principles could be applied in many other countries and to many other areas of genomic medicine.

Evaluating the survivor or the relatives of those who do not survive: the role of genetic testing

2017 ◽  
Vol 27 (S1) ◽  
pp. S19-S24 ◽  
Author(s):  
David J. Tester ◽  
Michael J. Ackerman
Keyword(s):  
Genetic Testing ◽  
Genetic Basis ◽  
Genetic Disorders ◽  
Genomic Medicine ◽  
Mendelian Inheritance ◽  
Societal Implications ◽  
Clinical Genetic ◽  
Clinical Genetic Testing ◽  
Specific Impact

AbstractThe molecular millennium has bestowed clinicians and researchers with the essential tools to identify the underlying genetic substrates for thousands of genetic disorders, most of which are rare and follow Mendelian inheritance patterns. The genetic basis of potentially lethal and heritable cardiomyopathies and cardiac channelopathies has been identified and are now better understood. Genetic testing for several of these heritable conditions has made its transition from discovery through translation and have been commercially available clinical tests for over a decade. Now that clinical genetic testing is available more readily and delivers a disease-specific impact across the triad of medicine – diagnostic, prognostic, and therapeutic – it is important for the community of cardiologists to not only be familiar with the language of genomic medicine but to also be wiser users and even wiser interpreters of genetic testing so that wise decisions can be rendered for those patients and their families being evaluated with respect to the presence or absence of one of these potentially lethal yet highly treatable genetic disorders. The purpose of this review is to provide the reader with a foundational understanding of genetic testing in clinical cardiology. Here, we will present some benefits of genetic testing: indications for either post-mortem genetic testing for the major cardiomyopathies and channelopathies or pre-mortem genetic testing among the decedent’s surviving relatives; the need for careful interpretation of genetic testing results; the importance of genetic counselling; and some points on the ethical and societal implications of genetic testing.

Ethical Aspects of Genetic Testing

2001 ◽  
Vol 3 (1) ◽  
pp. 24-32 ◽  
Author(s):  
Michele A. Carter
Keyword(s):  
Genetic Testing ◽  
Predictive Testing ◽  
Fundamental Rights ◽  
Inherited Disease ◽  
Ethical Aspects ◽  
Ethical Guidelines ◽  
Ethical Concerns ◽  
Legal Challenges ◽  
Clinical Practice Setting ◽  
Research Findings

This article explores ethical concerns and emerging dilemmas associated with the proliferation of information resulting fromthe extraordinary advances in molecular genetics. It provides an overviewof the ethical and legal challenges associated with predictive testing for inherited disease currently being addressed in the literature. Finally, it offers a framework of ethical principles that can be used to guide nurses and other practitioners in the appropriate application of research findings to the clinical practice setting. The ethical guidelines of self-determination, benefit-burden ratio, and justice promulgated in The Belmont Report are interpreted in the new context of predictive genetic testing. The author concludes by discussing how to balance the technical imperative to advance genetic knowledge for the sake of human health with the ethical imperative to preserve the fundamental rights and liberties of both individuals and communities who are its recipients.

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications

2021 ◽  
Author(s):  
David R. Murdock ◽  
Eric Venner ◽  
Donna M. Muzny ◽  
Ginger A. Metcalf ◽  
Mullai Murugan ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Management ◽  
High Rate ◽  
Management Implications

scholarly journals Educational Case: Pancreatic Cystic Disease: A Multimodal Diagnostic Approach to Determine Clinical Management

2021 ◽  
Vol 8 ◽  
pp. 237428952199803
Author(s):  
Daniel Geisler ◽  
Samer N. Khader
Keyword(s):  
Medical Education ◽  
Clinical Management ◽  
Organ System ◽  
Learning Objectives ◽  
National Standards ◽  
Cystic Disease ◽  
Full List ◽  
Additional Information ◽  
Disease Mechanisms ◽  
Basic Competencies

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1

scholarly journals Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

2021 ◽  
Author(s):  
Michael Abbott ◽  
Lynda McKenzie ◽  
Blanca Viridiana Guizar Moran ◽  
Sebastian Heidenreich ◽  
Rodolfo Hernández ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Genetic Testing ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Diseases ◽  
Genomic Medicine ◽  
Future Research ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Peace Of Mind

AbstractNovel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study. We also explored what users value about genomic sequencing. Insights from the costing and value assessments will inform a subsequent economic evaluation of genomic medicine in Scotland. An average cost of £1,841 per singleton was estimated for the standard genetic testing pathway, with significant variability between phenotypes. WGS cost £6625 per family trio, but this estimate reflects the use of WGS during the SGP project and large cost savings may be realised if sequencing was scaled up. Patients and families valued (i) the chance of receiving a diagnosis (and the peace of mind and closure that brings); (ii) the information provided by WGS (including implications for family planning and secondary findings); and (iii) contributions to future research. Our costings will be updated to address limitations of the current study for incorporation in budget impact modelling and cost-effectiveness analysis (cost per diagnostic yield). Our insights into the benefits of WGS will guide the development of a discrete choice experiment valuation study. This will inform a user-perspective cost–benefit analysis of genome-wide sequencing, accounting for the broader non-health outcomes. Taken together, our research will inform the long-term strategic development of NHS Scotland clinical genetics testing services, and will be of benefit to others seeking to undertake similar evaluations in different contexts.

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