Cardiomyopathy

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UNIVERSITY OF MINNESOTA PHYSICIANS OUTREACH LABS Submit this form along with the appropriate MOLECULAR DIAGNOSTICS (612) 273-8445 Molecular requisition (Molecular Diagnostics or DATE: TIME COLLECTED: PCU/CLINIC: Molecular NGS Oncology). AM PM PATIENT IDENTIFICATION DIAGNOSIS (Dx) / DIAGNOSIS CODES (ICD-9) - OUTPATIENTS ONLY SPECIMEN TYPE: o Blood (1) (2) (3) (4) PLEASE COLLECT 5-10CC IN ACD-A OR EDTA TUBE ORDERING PHYSICIAN NAME AND PHONE NUMBER: Tests can be ordered as a full panel, or by individual gene(s). Please contact the genetic counselor with any questions at 612-624-8948 or by pager at 612-899-3291. _______________________________________________ Test Ordered- EPIC: Next generation sequencing(Next Gen) Sunquest: NGS Brugada syndrome DMD Aortopathy Full panel DNAJC19 SCN5A DSP Full panel GPD1L Cardiomyopathy, familial MYH11 CACNA1C hypertrophic ACTA2 SCN1B Full panel MYLK KCNE3 ANKRD1 FBN2 SCN3B JPH2 SLC2A10 HCN4 PRKAG2 COL5A2 MYH7 COL5A1 MYL2 COL3A1 Cardiomyopathy ACTC1 CBS Cardiomyopathy, dilated CSRP3 SMAD3 Full panel TNNC1 TGFBR1 LDB3 MYH6 TGFBR2 LMNA VCL FBN1 ACTN2 MYOZ2 Arrhythmogenic right ventricular DSG2 PLN dysplasia NEXN CALR3 TNNT2 TNNT2 NEXN Full panel RBM20 TPM1 TGFB3 SCN5A MYBPC3 DSG2 MYH6 TNNI3 DSC2 TNNI3 MYL3 JUP TTN TTN RYR2 BAG3 MYLK2 TMEM43 DES Cardiomyopathy, familial DSP CRYAB EYA4 restrictive PKP2 Full panel Atrial fibrillation LAMA4 MYPN TNNI3 SGCD MYPN TNNT2 Full panel CSRP3 SCN5A MYBPC3 GJA5 TCAP ABCC9 ABCC9 SCN1B PLN SCN2B ACTC1 KCNQ1 MYH7 KCNE2 TMPO NPPA VCL NPPA TPM1 KCNA5 TNNC1 KCNJ2 GATAD1 4/1/2014 Version 1 Heart block Congenital heart SCN5A Syndromes defects TRPM4 Alagille syndrome Left ventricular noncompaction JAG1 Aortic supravalvular stenosis TAZ Andersen syndrome ELN DTNA KCNJ2 Aortic valve disease MYBPC3 Barth syndrome NOTCH1 LDB3 TAZ SMAD6 ACTC1 Danon disease ASD with heterotaxy MYH7 LAMP2 CRELD1 TNNT2 Emery-Dreifuss muscular dystrophy Atrial septal defect 2 TPM1 EMD Full panel Lipid disease LMNA GATA4 LPL Fabry disease, cardiac variant MYH6 LDLR GLA TBX20 PCSK9 Holt-Oram syndrome ACTC1 LDLRAP1 TBX5 TLL1 ANGPTL3 Noonan syndrome NKX2-5 LMF1 Full panel CITED2 ABCA1 MAP2K1 Atrioventricular septal defect 2 Long QT syndrome MAP2K2 Full panel Full panel HRAS CRELD1 KCNE2 PTPN11 GJA1 SNTA1 KRAS GATA4 KCNJ5 SOS1 GATA6 KCNQ1 RAF1 Congenital heart defects SCN4B NRAS TAB2 AKAP9 BRAF Conotruncal heart malformations KCNH2 SHOC2 NKX2-5 SCN5A Sengers syndrome Hypoplastic left heart syndrome 1 ANK2 AGK Full panel KCNE1 Timothy syndrome GJA1 CAV3 CACNA1C NKX2-5 Pulmonary hypertension Persistent truncus arteriosus BMPR2 NKX2-6 SMAD9 Tetralogy of Fallot Short QT syndrome Ventricular fibrillation Full panel Full panel DPP6 TBX1 KCNH2 SCN5A NKX2-5 KCNQ1 CASQ2 Transposition of the great arteries, KCNJ2 RYR2 dextro-looped 1 Sick sinus syndrome CASQ2 MED13L Full panel CALM1 Ventricular septal defect SCN5A TRDN Full panel HCN4 Wolff-Parkinson-White syndrome GATA4 MYH6 PRKAG2 CITED2 4/1/2014 Version 1 .

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FLNC Missense Variants in Familial Noncompaction Cardiomyopathy
Cardiogenetics 2019; volume 9:8181 FLNC missense variants than 2 according to current echocardio- in familial noncompaction graphic criteria, or 2.3 on CMR.1,2 Correspondence: Jaap I. van Waning, Approximately 10% of patients diagnosed Department of Clinical Genetics, EE 2038, cardiomyopathy with NCCM have concurrent congenital Erasmus MC, POB 2040, 3000CA Rotterdam, heart defects (CHD).3,4 the Netherlands. Tel.: +3107038388 - Fax: +3107043072. Jaap I. van Waning,1 In 30-40% of cases diagnosed with E-mail: [email protected] Yvonne M. Hoedemaekers,2 NCCM a pathogenic variant can be identi- 2,3 4 Wouter P. te Rijdt, Arne I. Jpma, fied. Around 80% of these pathogenic vari- Acknowledgements: JVW was supported by a Daphne Heijsman,4 Kadir Caliskan,5 ants involve the same sarcomere genes, that grant from the Jaap Schouten Foundation. Elke S. Hoendermis,6 are the major causes for hypertrophic car- WPTR was supported by a Young Talent Program (CVON PREDICT) grant 2017T001 Tineke P. Willems,7 diomyopathy (HCM) and dilated cardiomy- - Dutch Heart Foundation. 8 opathy (DCM), in particular MYH7, Arthur van den Wijngaard, 5,6 3 MYBPC3 and TTN. Filamin C (FLNC) Albert Suurmeijer, Conflict of interest: the authors declare no plays a central role in muscle functioning Marjon A. van Slegtenhorst,1 potential conflict of interest. by maintaining the structural integrity of the Jan D.H. Jongbloed,2 muscle fibers. Pathogenic variants in FLNC Received for publication: 20 March 2019. Danielle F. Majoor-Krakauer,1 2 were found to be associated with a wide Revision received: 29 July 2019. Paul A.
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Post-Mortem Whole-Exome Analysis in a Large Sudden Infant Death Syndrome Cohort with a Focus on Cardiovascular and Metabolic Genetic Diseases
European Journal of Human Genetics (2017) 25, 404–409 & 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1018-4813/17 www.nature.com/ejhg ARTICLE Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases Jacqueline Neubauer*,1, Maria Rita Lecca2, Giancarlo Russo2, Christine Bartsch3, Argelia Medeiros-Domingo4, Wolfgang Berger5,6,7 and Cordula Haas1 Sudden infant death syndrome (SIDS) is described as the sudden and unexplained death of an apparently healthy infant younger than one year of age. Genetic studies indicate that up to 35% of SIDS cases might be explained by familial or genetic diseases such as cardiomyopathies, ion channelopathies or metabolic disorders that remained undetected during conventional forensic autopsy procedures. Post-mortem genetic testing by using massive parallel sequencing (MPS) approaches represents an efﬁcient and rapid tool to further investigate unexplained death cases and might help to elucidate pathogenic genetic variants and mechanisms in cases without a conclusive cause of death. In this study, we performed whole-exome sequencing (WES) in 161 European SIDS infants with focus on 192 genes associated with cardiovascular and metabolic diseases. Potentially causative variants were detected in 20% of the SIDS cases. The majority of infants had variants with likely functional effects in genes associated with channelopathies (9%), followed by cardiomyopathies (7%) and metabolic diseases (1%). Although lethal arrhythmia represents the most plausible and likely cause of death, the majority of SIDS cases still remains elusive and might be explained by a multifactorial etiology, triggered by a combination of different genetic and environmental risk factors.
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The Cytoskeleton in Cell-Autonomous Immunity: Structural Determinants of Host Defence
Mostowy & Shenoy, Nat Rev Immunol, doi:10.1038/nri3877 The cytoskeleton in cell-autonomous immunity: structural determinants of host defence Serge Mostowy and Avinash R. Shenoy Medical Research Council Centre of Molecular Bacteriology and Infection (CMBI), Imperial College London, Armstrong Road, London SW7 2AZ, UK. e‑mails: [email protected] ; [email protected] doi:10.1038/nri3877 Published online 21 August 2015 Abstract Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton — actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement — have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence. 1 Mostowy & Shenoy, Nat Rev Immunol, doi:10.1038/nri3877 Cell-autonomous immunity, which is defined as the ability of a host cell to eliminate an invasive infectious agent, is a first line of defence against microbial pathogens 1 . It relies on antimicrobial proteins, specialized degradative compartments and programmed host cell death 1–3 . Cell- autonomous immunity is mediated by tiered innate immune signalling networks that sense microbial pathogens and stimulate downstream pathogen elimination programmes. Recent studies on host– microorganism interactions show that components of the host cell cytoskeleton are integral to the detection of bacterial pathogens as well as to the mobilization of antibacterial responses (FIG.
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Genetic Variation Screening of TNNT2 Gene in a Cohort of Patients with Hypertrophic and Dilated Cardiomyopathy
Physiol. Res. 61: 169-175, 2012 https://doi.org/10.33549/physiolres.932157 Genetic Variation Screening of TNNT2 Gene in a Cohort of Patients With Hypertrophic and Dilated Cardiomyopathy M. JÁCHYMOVÁ1, A. MURAVSKÁ1, T. PALEČEK2, P. KUCHYNKA2, H. ŘEHÁKOVÁ1, S. MAGAGE2, A. KRÁL2, T. ZIMA1, K. HORKÝ2, A. LINHART2 1Institute of Clinical Chemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic, 2Second Department of Internal Medicine – Clinical Department of Cardiology and Angiology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic Received February 1, 2011 Accepted October 17, 2011 On-line January 31, 2012 Summary Introduction Mutations in troponin T (TNNT2) gene represent the important part of currently identified disease-causing mutations in Cardiomyopathies are generally defined as hypertrophic (HCM) and dilated (DCM) cardiomyopathy. The aim myocardial disorders in which the heart muscle is of this study was to analyze TNNT2 gene exons in patients with structurally and functionally abnormal, in the absence of HCM and DCM diagnosis to improve diagnostic and genetic coronary artery disease, hypertension, valvular disease consultancy in affected families. All 15 exons and their flanking and congenital heart disease sufficient to cause the regions of the TNNT2 gene were analyzed by DNA sequence observed myocardial abnormality (Elliott et al. 2008). analysis in 174 patients with HCM and DCM diagnosis. We According to the morphological and functional phenotype identified genetic variations in TNNT2 exon regions in 56 patients the diagnosis of hypertrophic and dilated cardiomyopathy and genetic variations in TNNT2 intron regions in 164 patients.
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Genetic Mutations and Mechanisms in Dilated Cardiomyopathy
Genetic mutations and mechanisms in dilated cardiomyopathy Elizabeth M. McNally, … , Jessica R. Golbus, Megan J. Puckelwartz J Clin Invest. 2013;123(1):19-26. https://doi.org/10.1172/JCI62862. Review Series Genetic mutations account for a significant percentage of cardiomyopathies, which are a leading cause of congestive heart failure. In hypertrophic cardiomyopathy (HCM), cardiac output is limited by the thickened myocardium through impaired filling and outflow. Mutations in the genes encoding the thick filament components myosin heavy chain and myosin binding protein C (MYH7 and MYBPC3) together explain 75% of inherited HCMs, leading to the observation that HCM is a disease of the sarcomere. Many mutations are “private” or rare variants, often unique to families. In contrast, dilated cardiomyopathy (DCM) is far more genetically heterogeneous, with mutations in genes encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. DCM is characterized by enlarged ventricular dimensions and impaired systolic and diastolic function. Private mutations account for most DCMs, with few hotspots or recurring mutations. More than 50 single genes are linked to inherited DCM, including many genes that also link to HCM. Relatively few clinical clues guide the diagnosis of inherited DCM, but emerging evidence supports the use of genetic testing to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia. Find the latest version: https://jci.me/62862/pdf Review series Genetic mutations and mechanisms in dilated cardiomyopathy Elizabeth M. McNally, Jessica R. Golbus, and Megan J. Puckelwartz Department of Human Genetics, University of Chicago, Chicago, Illinois, USA. Genetic mutations account for a significant percentage of cardiomyopathies, which are a leading cause of conges- tive heart failure.
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Minding the Calcium Store: Ryanodine Receptor Activation As a Convergent Mechanism of PCB Toxicity
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Next Generation Sequencing for Molecular Confirmation of Hereditary
Arch Cardiol Mex. 2015;85(1):68---72 www.elsevier.com.mx SPECIAL ARTICLE Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes a,∗ b b b Manlio F. Márquez , David Cruz-Robles , Selene Ines-Real , Gilberto Vargas-Alarcón , a Manuel Cárdenas a Departamento de Electrofisiología, Instituto Nacional de Cardiología Ignacio Chávez, México, D.F., Mexico b Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, México, D.F., Mexico Received 26 March 2014; accepted 8 December 2014 KEYWORDS Abstract Hereditary sudden cardiac death syndromes comprise a wide range of diseases result- Arrhythmias; ing from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse Hereditary sudden mutations that cause the altered encoding of the diverse proteins constituting these channels, cardiac death thus affecting directly the currents of the corresponding ions. In the present article we will syndromes; briefly review how to arrive to a clinical diagnosis and we will present the results of molecular Right ventricle genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National arrhythmogenic Institute of Cardiology of Mexico City. cardiomyopathy; © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México Brugada syndrome S.A. All rights reserved. PALABRAS CLAVE Confirmación diagnóstica molecular mediante secuenciación masiva de nueva Arritmias; generación (‘‘next generation sequencing’’) en síndromes hereditarios de muerte Síndromes súbita cardíaca hereditarios de Resumen Los síndromes hereditarios de muerte súbita cardíaca comprenden una amplia gama muerte súbita; Displasia de enfermedades resultantes de la alteración en los canales iónicos cardíacos. Los genes implicados en estos síndromes presentan mutaciones que causan alteraciones de las diversas Arritmogénica del proteínas que constituyen estos canales y que, por lo tanto, afectan directamente a las difer- ventriculo derecho; entes corrientes iónicas.
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Sarcomere Gene Variants Act As a Genetic Trigger Underlying the Development of Left Ventricular Noncompaction
www.nature.com/pr BASIC SCIENCE ARTICLE Sarcomere gene variants act as a genetic trigger underlying the development of left ventricular noncompaction Asami Takasaki1, Keiichi Hirono1, Yukiko Hata2, Ce Wang1,3, Masafumi Takeda4, Jun K Yamashita4, Bo Chang1, Hideyuki Nakaoka1, Mako Okabe1, Nariaki Miyao1, Kazuyoshi Saito1, Keijiro Ibuki1, Sayaka Ozawa1, Michikazu Sekine5, Naoki Yoshimura6, Naoki Nishida2, Neil E. Bowles7 and Fukiko Ichida1 BACKGROUND: Left ventricular noncompaction (LVNC) is a primary cardiomyopathy with heterogeneous genetic origins. The aim of this study was to elucidate the role of sarcomere gene variants in the pathogenesis and prognosis of LVNC. METHODS AND RESULTS: We screened 82 Japanese patients (0–35 years old), with a diagnosis of LVNC, for mutations in seven genes encoding sarcomere proteins, by direct DNA sequencing. We identiﬁed variants in a signiﬁcant proportion of cases (27%), which were associated with poor prognosis (p = 0.012), particularly variants in TPM1, TNNC1, and ACTC1 (p = 0.012). To elucidate the pathological role, we developed and studied human-induced pluripotent stem cells (hiPSCs) from a patient carrying a TPM1 p. Arg178His mutation, who underwent heart transplantation. These cells displayed pathological changes, with mislocalization of tropomyosin 1, causing disruption of the sarcomere structure in cardiomyocytes, and impaired calcium handling. Microarray analysis indicated that the TPM1 mutation resulted in the down-regulation of the expression of numerous genes involved in heart development, and positive regulation of cellular process, especially the calcium signaling pathway. CONCLUSIONS: Sarcomere genes are implicated as genetic triggers in the development of LVNC, regulating the expression of numerous genes involved in heart development, or modifying the severity of disease.
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Non-Coding Rnas in the Cardiac Action Potential and Their Impact on Arrhythmogenic Cardiac Diseases
Review Non-Coding RNAs in the Cardiac Action Potential and Their Impact on Arrhythmogenic Cardiac Diseases Estefania Lozano-Velasco 1,2 , Amelia Aranega 1,2 and Diego Franco 1,2,* 1 Cardiovascular Development Group, Department of Experimental Biology, University of Jaén, 23071 Jaén, Spain; [email protected] (E.L.-V.); [email protected] (A.A.) 2 Fundación Medina, 18016 Granada, Spain * Correspondence: [email protected] Abstract: Cardiac arrhythmias are prevalent among humans across all age ranges, affecting millions of people worldwide. While cardiac arrhythmias vary widely in their clinical presentation, they possess shared complex electrophysiologic properties at cellular level that have not been fully studied. Over the last decade, our current understanding of the functional roles of non-coding RNAs have progressively increased. microRNAs represent the most studied type of small ncRNAs and it has been demonstrated that miRNAs play essential roles in multiple biological contexts, including normal development and diseases. In this review, we provide a comprehensive analysis of the functional contribution of non-coding RNAs, primarily microRNAs, to the normal conﬁguration of the cardiac action potential, as well as their association to distinct types of arrhythmogenic cardiac diseases. Keywords: cardiac arrhythmia; microRNAs; lncRNAs; cardiac action potential Citation: Lozano-Velasco, E.; Aranega, A.; Franco, D. Non-Coding RNAs in the Cardiac Action Potential 1. The Electrical Components of the Adult Heart and Their Impact on Arrhythmogenic The adult heart is a four-chambered organ that propels oxygenated blood to the entire Cardiac Diseases. Hearts 2021, 2, body. It is composed of atrial and ventricular chambers, each of them with distinct left and 307–330.
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Novel Pathogenic Variants in Filamin C Identified in Pediatric Restrictive Cardiomyopathy
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Development of the Stria Vascularis and Potassium Regulation in the Human Fetal Cochlea: Insights Into Hereditary Sensorineural Hearing Loss
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