Unveiling Mechanisms Involved in Non-traditional Cases of Inherited Cardiac Channelopathies - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Unveiling Mechanisms Involved in Non-traditional Cases of Inherited Cardiac Channelopathies write by Malcolm Hoshi. This book was released on 2015. Unveiling Mechanisms Involved in Non-traditional Cases of Inherited Cardiac Channelopathies available in PDF, EPUB and Kindle. Cardiac arrhythmias are diseases of electrical rhythm that can lead to sudden cardiac death. Inherited arrhythmias can strike any age group, and are a leading cause of sudden death among young people. Many of these are caused by mutations in ion channels, proteins which govern the flow of electricity through the heart. As these are genetic mutations, we are able to use genetic testing to determine who may be at risk, and to prophylactically treat them accordingly. However, a common feature of cardiac arrhythmias is genotype-phenotype discordance. This means that, for various reasons, carrying a disease-causing mutation does not ensure a disease phenotype. When one considers genotype-phenotype discordance in the light of the fact that treatments such as the implantation of a cardiodefibrillator carry significant cost and risk, it is clear that a difficult proposition faces medical professionals in balancing over- and under-treatment. Thus, the overall aim of my dissertation is to improve the diagnostic ability of clinicians when presented with an individual who has a mutation in a cardiac ion channel. My first project approaches this by examining the fidelity of clinical genetic testing in calling pathogenic mutations in the context of Long QT Syndrome. I present an interesting case of a family which carries three potential mutations and show via electrophysiology and computer modeling that it is likely a combination of all three that causes disease. For my second project, I look more closely at potential mechanisms of genotype-phenotype discordance in the context of another arrhythmia, Brugada Syndrome. Specifically, I characterize a novel mechanism using electrophysiology and biochemistry whereby apparently benign mutations in NaV1.5 can lead to a loss-of-function. These mutations do not show any defects when expressed alone, but by interaction with a wild-type protein lead to a loss-of-function. In summary, my work overall shows that biophysical characterization of mutations remains the best tool for predicting risk in genetic arrhythmias, and I also present a novel mechanism to help explain the high degree of variability seen in inherited arrhythmias.
Ion Channel Diseases
Ion Channel Diseases - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Ion Channel Diseases write by . This book was released on 2011-09-06. Ion Channel Diseases available in PDF, EPUB and Kindle. Ion channel dysfunction in humans leads to impairment of the excitable processes necessary for the normal function of several tissues, such as muscle and brain. It follows that an increasing number of human diseases have been associated with malfunctioning ion channels, many of which have a genetic component. This volume of Advances in Genetics presents a broad and comprehensive overview of the inherited channelopathies in humans, including clinical, genetic and molecular aspects of these conditions. Keeping true to the scope of the serial, novel genomic and modeling research approaches and a review of potential therapeutic approaches for each of these conditions are also incorporated.
J Wave Syndromes
J Wave Syndromes - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook J Wave Syndromes write by Charles Antzelevitch. This book was released on 2016-06-27. J Wave Syndromes available in PDF, EPUB and Kindle. This book delineates the state of the art of the diagnosis and treatment of J wave syndromes, as well as where future research needs to be directed. It covers basic science, translational and clinical aspects of these syndromes. The authors are leading experts in their respective fields, who have contributed prominently to the literature concerning these topics. J wave syndromes are one of the hottest topics in cardiology today. Cardiac arrhythmias associated with Brugada syndrome (BrS) or an early repolarization (ER) pattern in the inferior or infero-lateral ECG leads are thought to be mechanistically linked to accentuation of transient outward current (Ito)-mediated J waves. Although BrS and ER syndrome (ERS) differ with respect to magnitude and lead location of abnormal J waves, they are thought to represent a continuous spectrum of phenotypic expression termed J wave syndromes. ERS is divided into three subtypes with the most severe, Type 3, displaying an ER pattern globally in the inferior, lateral and right precordial leads. BrS has been linked to mutations in 19 different genes, whereas ERS has been associated with mutations in 7 different genes. There is a great deal of confusion as to how to properly diagnose and treat the J wave syndromes as well as confusion about the underlying mechanisms. The demonstration of successful epicardial ablation of BrS has provided new therapeutic options for the management of this syndrome for which treatment alternatives are currently very limited, particularly in the case of electrical storms caused by otherwise uncontrollable recurrent VT/VF. An early repolarization pattern is observed in 2-5% of the US population. While it is clear that the vast majority of individuals exhibiting an ER pattern are not at risk for sudden cardiac death, the challenge moving forward is to identify those individuals who truly are at risk and to design safe and effective treatments.
Ventricular Arrhythmias
Ventricular Arrhythmias - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Ventricular Arrhythmias write by John M. Miller. This book was released on 2008. Ventricular Arrhythmias available in PDF, EPUB and Kindle. Ventricular arrhythmias cause most cases of sudden cardiac death, which is the leading cause of death in the US. This issue reviews the causes of arrhythmias and the promising new drugs and devices to treat arrhythmias.
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease write by Roger N. Rosenberg. This book was released on 2014-10-28. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease available in PDF, EPUB and Kindle. Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Fifth Edition provides a comprehensive introduction and reference to the foundations and key practical aspects relevant to the majority of neurologic and psychiatric disease. A favorite of over three generations of students, clinicians and scholars, this new edition retains and expands the informative, concise and critical tone of the first edition. This is an essential reference for general medical practitioners, neurologists, psychiatrists, geneticists, and related professionals, and for the neuroscience and neurology research community. The content covers all aspects essential to the practice of neurogenetics to inform clinical diagnosis, treatment and genetic counseling. Every chapter has been thoroughly revised or newly commissioned to reflect the latest scientific and medical advances by an international team of leading scientists and clinicians. The contents have been expanded to include disorders for which a genetic basis has been recently identified, together with abundant original illustrations that convey and clarify the key points of the text in an attractive, didactic format. Previous editions have established this book as the leading tutorial reference on neurogenetics. Researchers will find great value in the coverage of genomics, animal models and diagnostic methods along with a better understanding of the clinical implications. Clinicians will rely on the coverage of the basic science of neurogenetics and the methods for evaluating patients with biochemical abnormalities or gene mutations, including links to genetic testing for specific diseases. Comprehensive coverage of the neurogenetic foundation of neurological and psychiatric disease Detailed introduction to both clinical and basic research implications of molecular and genetic understanding of the brain Detailed coverage of genomics, animal models and diagnostic methods with new coverage of evaluating patients with biochemical abnormalities or gene mutations
