scholarly journals MYH9 Genetic Variants Associated With Glomerular Disease: What Is the Role for Genetic Testing?

2010 ◽  
Vol 30 (4) ◽  
pp. 409-417 ◽  
Author(s):  
Jeffrey B. Kopp ◽  
Cheryl A. Winkler ◽  
George W. Nelson
Keyword(s):  
Genetic Testing ◽  
Genetic Variants ◽  
Glomerular Disease

scholarly journals Personalized Nutrition for Management of Micronutrient Deficiency—Literature Review in Non-bariatric Populations and Possible Utility in Bariatric Cohort

2020 ◽  
Vol 30 (9) ◽  
pp. 3570-3582
Author(s):  
Shannon Galyean ◽  
Dhanashree Sawant ◽  
Andrew C. Shin
Keyword(s):  
Bariatric Surgery ◽  
Morbid Obesity ◽  
Genetic Testing ◽  
High Risk ◽  
Genetic Variants ◽  
Micronutrient Deficiency ◽  
High Dose ◽  
Micronutrient Deficiencies ◽  
Personalized Nutrition

Abstract Background Bariatric surgery can effectively treat morbid obesity; however, micronutrient deficiencies are common despite recommendations for high-dose supplements. Genetic predisposition to deficiencies underscores necessary identification of high-risk candidates. Personalized nutrition (PN) can be a tool to manage these deficiencies. Methods Medline, PubMed, and Google Scholar were searched. Articles involving genetic testing, micronutrient metabolism, and bariatric surgery were included. Results Studies show associations between genetic variants and micronutrient metabolism. Research demonstrates genetic testing to be a predictor for outcomes among obesity and bariatric surgery populations. There is limited research in bariatric surgery and micronutrient genetic variants. Conclusion Genotype-based PN is becoming feasible to provide an effective treatment of micronutrient deficiencies associated with bariatric surgery. The role of genomic technology in micronutrient recommendations needs further investigation.

scholarly journals 9p21 and the Genetic Revolution for Coronary Artery Disease

2012 ◽  
Vol 58 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Robert Roberts ◽  
Alexandre F R Stewart
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Genetic Testing ◽  
Coronary Artery ◽  
Genetic Variants ◽  
Genetic Factors ◽  
Genomic Study ◽  
Increased Risk ◽  
Artery Disease

Abstract BACKGROUND It has long been recognized that 50% of the susceptibility for coronary artery disease (CAD) is due to predisposing genetic factors. Comprehensive prevention is likely to require knowledge of these genetic factors. CONTENT Using a genomewide association study (GWAS), the Ottawa Heart Genomic Study and the deCODE group simultaneously identified the first genetic risk variant, at chromosome 9p21. The 9p21 variant became the first risk factor to be identified since 1964. 9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 2-fold increase in risk, similar to that of smoking and cholesterol. Routine genetic testing will probably remain controversial until a specific treatment is developed. Over a period of 5 years, however, GWASs have identified 30 genetic variants for CAD risk, of which only 6 act through the known risk factors. SUMMARY The 9p21 variant has now been established as an independent risk factor for CAD and, along with the additional 29 risk genetic variants recently identified, is likely to provide the thrust for genetic testing and personalized medicine in the near future.

1269The SADS heart of the matter: a review of the sudden arrhythmic death syndrome (SADS) biobank - the cornerstone of a national strategy

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
J Carron ◽  
J O"brien ◽  
K Heverin ◽  
M Gallagher ◽  
M Fitzgibbon ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Variants ◽  
Class Iii ◽  
Cascade Screening ◽  
Detection Rates ◽  
Molecular Autopsy ◽  
Family Screening ◽  
First Degree Relatives ◽  
Uncertain Significance ◽  
Class Iv

Abstract Background Sudden cardiac death (SCD) in the young (age 1-35) is commonly attributed to structural and arrhythmogenic syndromes, for which there is often an underlying genetic basis. Expert recommendation emphasises the importance of genetic testing in such cases, however to date this remains the first and only national programme in Europe to facilitate this.  Aim  To review detection rates of genetic variants in samples tested via the SADS BioBank and possibly demonstrate the merits of this novel resource for primary prevention for family members. Methods  Family screening and consent for genetic testing was carried out in the Family Heart Screening Clinic. Result analysis of samples sent for molecular autopsy via the BioBank from its induction in January 2015 was performed. Genetic analysis was conducted via the same internationally accredited next generation sequencing lab. Results  From January 2015 to July 2019, 161 samples had been stored in the SADS BioBank following confirmed SADS death on autopsy; 33% female and 67% male. Of these, 24 (14.9%) samples were sent for genetic testing: 21 for a 380 gene molecular autopsy and 3 for a targeted hypertrophic cardiomyopathy panel (173 genes). Of 24 samples tested, 10 (42%) yielded positive genetic variants: 4 American College of Medical Genetics (ACMG) Class IV or V mutations considered pathogenic, and 6 ACMG class III variants of uncertain significance (VUS). Familial cascade screening following confirmed pathogenic mutations resulted in detection of 3 (33.3%) positive genotypes in 9 first-degree relatives. Screening of relatives of Class III positive probands resulted in diagnosis of an Inherited Cardiac Condition (ICC) in 25% of first-degree relatives. 8.2% of first-degree relatives of probands with negative gene testing were given an ICC diagnosis following clinical screening. Conclusions  This short study demonstrates the unique potential the SADS BioBank has to offer in terms of identifying those most at risk and optimising prevention strategies for relatives, thus highlighting the role for such a resource in terms of preventative screening in the future. Pathogenic Variant (ACMG Class IV & V) Variant of Uncertain Significance(ACMG Class III) No Gene Variant Identified Number Detected (n = 24) 4 6 14 1st Degree Relatives Screened (n = 86) 17 20 49 2nd Degree Relatives Screened (n = 46) 4 23 19 Genotype Detected (n = 4) 3 1 0 Phenotype Detected (n = 10) 1 5 4 Breakdown of clinical and genetic results of family screening by ACMG class. Abstract Figure.

scholarly journals Can Genetic Testing Identify Talent for Sport?

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 972 ◽  
Author(s):  
Craig Pickering ◽  
John Kiely ◽  
Jozo Grgic ◽  
Alejandro Lucia ◽  
Juan Del Coso
Keyword(s):  
Genetic Testing ◽  
Genetic Variants ◽  
Genetic Information ◽  
Elite Athlete ◽  
Disease Prediction ◽  
Prediction Tool ◽  
Accurate Identification ◽  
Psychological Traits ◽  
Heritable Trait ◽  
And Training

Elite athlete status is a partially heritable trait, as are many of the underpinning physiological, anthropometrical, and psychological traits that contribute to elite performance. In recent years, our understanding of the specific genetic variants that contribute to these traits has grown, such that there is considerable interest in attempting to utilise genetic information as a tool to predict future elite athlete status. In this review, we explore the extent of the genetic influence on the making of a sporting champion and we describe issues which, at present, hamper the utility of genetic testing in identifying future elite performers. We build on this by exploring what further knowledge is required to enhance this process, including a reflection on the potential learnings from the use of genetics as a disease prediction tool. Finally, we discuss ways in which genetic information may hold utility within elite sport in the future, including guiding nutritional and training recommendations, and assisting in the prevention of injury. Whilst genetic testing has the potential to assist in the identification of future talented performers, genetic tests should be combined with other tools to obtain an accurate identification of those athletes predisposed to succeed in sport. The use of total genotype scores, composed of a high number of performance-enhancing polymorphisms, will likely be one of the best strategies in the utilisation of genetic information to identify talent in sport.

scholarly journals Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

2017 ◽  
Author(s):  
Houria Daimi ◽  
Amel Haj Khelil ◽  
Ali Neji ◽  
Khaldoun Ben Hamda ◽  
Sabri Maaoui ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Binding Site ◽  
Candidate Genes ◽  
Brugada Syndrome ◽  
Genetic Variants ◽  
Sequence Variant ◽  
Α Subunit ◽  
Coding Sequence ◽  
Cardiac Sodium Channel ◽  
Scn5a Gene

AbstractBrugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3) in the absence of structural heart disease. This pattern is spontaneous, or is unmasked by intravenous administration of Class I antiarrhythmic drugs. The SCN5A-encoded α-subunit of the NaV1.5 cardiac sodium channel has been linked to BrS, and mutations in SCN5A are identified in 15–30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of protein-coding portions and flanking intronic regions of SCN5A, according to recent international guidelines. This excludes the regulatory untranslated regions (5’UTR and 3’UTR) from the routine genetic testing of BrS patients. We here screened the coding sequence, the flanking intronic regions as well as the 5’ and 3’UTR regions of SCN5A gene and further five candidate genes (GPD1L, SCN1B, KCNE3, SCN4B, and MOG1) in a Tunisian family diagnosed with Brugada syndrome.A new Q1000K mutation was identified on the SCN5A gene along with two common polymorphisms (H558R and D1819). Furthermore, multiple genetic variants were identified on the SCN5A 3’UTR, one of which is predicted to create additional microRNA (miRNAs) binding site for miR-1270. Additionally, we identified the hsa-miR-219a rs107822. No relevant coding sequence variant was identified in the remaining studied candidate genes. Although Q1000K is localized in the conserved binding site of MOG1 which predicts a functional consequence, this new mutation along with the additional variants were differentially distributed among the family members without any clear genotype-phenotype concordance. This gives extra evidences about the complexity of the disease and suggests that the occurrence and prognosis of BrS is most likely controlled by a combination of multiple genetic factors and exposures, rather than a single polymorphism/mutation. Most SCN5A polymorphisms were localized in non-coding regions hypothesizing an impact on the miRNA-target complementarities. In this regard, over-expression of miR-1270 led to a significant decrease of luciferase activity suggesting a direct role regulating SCN5A. Therefore, genetic variants that disrupt its binding affinity to SCN5A 3’UTR and/or its expression might cause loss of normal repression control and be associated to BrS.

scholarly journals Genetically Based Atrial Fibrillation: Current Considerations for Diagnosis and Management

2022 ◽  
Author(s):  
Anthony V. Pensa ◽  
Jayson R. Baman ◽  
Megan J. Puckelwartz ◽  
Jane Wilcox
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Testing ◽  
Genetic Variants ◽  
Early Onset ◽  
Association Studies ◽  
Single Gene ◽  
Risk Identification ◽  
Genome Wide Association Studies ◽  
Clinical Genetic ◽  
Common Genetic Variants

Atrial fibrillation (AF) is the most common atrial arrhythmia and is subcategorized into numerous clinical phenotypes. Given its heterogeneity, investigations into the genetic mechanisms underlying AF have been pursued in recent decades, with predominant analyses focusing on early onset or lone AF. Linkage analyses, genome wide association studies (GWAS), and single gene analyses have led to the identification of rare and common genetic variants associated with AF risk. Significant overlap with genetic variants implicated in dilated cardiomyopathy syndromes, including truncating variants of the sarcomere protein titin, have been identified through these analyses, in addition to other genes associated with cardiac structure and function. Despite this, widespread utilization of genetic testing in AF remains hindered by the unclear impact of genetic risk identification on clinical outcomes and the high prevalence of variants of unknown significance (VUS). However, genetic testing is a reasonable option for patients with early onset AF and in those with significant family history of arrhythmia. While many knowledge gaps remain, emerging data support genotyping to inform selection of AF therapeutics. In this review we highlight the current understanding of the complex genetic basis of AF and explore the overlap of AF with inherited cardiomyopathy syndromes. We propose a set of criteria for clinical genetic testing in AF patients and outline future steps for the integration of genetics into AF care.

Neurologists rarely perform genetic testing for Parkinson's disease. Evidence suggests that many patients with major genetic variants go undiagnosed

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Testing ◽  
Genetic Variants ◽  
Genetic Information ◽  
Low Cost ◽  
Psychological States ◽  
Key Stakeholders ◽  
Practice Care ◽  
Testing And Counseling

This review addresses the past and current states of genetic testing for Parkinson's disease based on the available data. In short, neurologists rarely perform genetic testing for Parkinson's disease, and evidence suggests that many patients with major genetic variants go undiagnosed. For patients, caregivers, and families, we looked into the various clinical and personal applications of genetic information. Consumer interest and demand for genetic testing in general, and for Parkinson's disease in particular, is increasing. Furthermore, researchers now have a better understanding of the genetic phenotypes of Parkinson's disease; there is more access to free or low-cost genetic testing and counseling; and patients with specific PD genetic variants can now participate in interventional clinical trials. All of these developments highlight the importance of expanding genetic testing for Parkinson's disease. By addressing perceived barriers and providing practical information and resources, we hope to increase clinician comfort and confidence, allowing them to offer more PD genetic testing in their practices. We can provide tailored information specific to the patient by entering the realm of personalized medicine, which, as other specialties have done, may result in improvements in clinical practice, care, and outcomes. Expanding PD genetic testing, on the other hand, will necessitate the collaboration of a group of medical experts and key stakeholders, particularly genetic counselors, who are already experts at guiding patients through complex genetic information and, more importantly, in the context of their psychological states.

scholarly journals Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report

2019 ◽  
Vol 56 (6) ◽  
pp. 347-357 ◽  
Author(s):  
Amanda B Spurdle ◽  
Stephanie Greville-Heygate ◽  
Antonis C Antoniou ◽  
Melissa Brown ◽  
Leslie Burke ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
Cancer Genetics ◽  
Rapid Expansion ◽  
Monogenic Disease ◽  
Common Disease ◽  
Variant Interpretation ◽  
Genetic Tests ◽  
Cancer Susceptibility Genes

The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.

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