An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome-Reference-Cited by-同舟云学术

An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome

Published:2020-02-11 Issue:6 Volume:141 Page:418-428
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Adler Arnon¹,Novelli Valeria²,Amin Ahmad S.³,Abiusi Emanuela²,Care Melanie¹,Nannenberg Eline A.⁴,Feilotter Harriet⁵,Amenta Simona²,Mazza Daniela²,Bikker Hennie⁴,Sturm Amy C.⁶,Garcia John⁷,Ackerman Michael J.⁸,Hershberger Raymond E.⁹,Perez Marco V.¹⁰,Zareba Wojciech¹¹,Ware James S.¹²¹³,Wilde Arthur A.M.³¹⁴,Gollob Michael H.¹¹⁵

Affiliation:

1. Division of Cardiology, Toronto General Hospital and University of Toronto, Canada (A.A, M.C., M.H.G.).

2. Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, and Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, Rome, Italy (V.N., E.A., S.A., D.M.).

3. Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences (A.S.A., A.A.M.W.), Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.

4. Department of Clinical Genetics (E.A.N., H.B.), Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.

5. Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Canada (H.F.).

6. Geisinger Genomic Medicine Institute, Danville, PA (A.C.S.).

7. Invitae Corporation, San Francisco, CA (J.G.).

8. Departments of Cardiovascular Diseases, Pediatrics, and Molecular Pharmacology and Experimental Therapeutics, Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Rochester, MN (M.J.A.).

9. Divisions of Human Genetics and Cardiovascular Medicine in the Department of Internal Medicine, Ohio State University, Columbus (R.E.H.).

10. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, CA (M.V.P.).

11. Cardiology Unit of the Department of Medicine, University of Rochester Medical Center, NY (W.Z.).

12. National Heart and Lung Institute and Medical Research Council London Institute of Medical Sciences, Imperial College London, UK (J.S.W.).

13. Royal Brompton and Harefield Hospitals National Health Service Trust, London, UK (J.S.W.).

14. Columbia University Irving Medical Center, New York (A.A.M.W.).

15. Department of Physiology, University of Toronto, and The Toronto General Hospital Research Institute, University Health Network, University of Toronto, Canada (M.H.G.).

Abstract

Background: Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition and are routinely tested in patients. Because of dramatic changes in our understanding of human genetic variation, reappraisal of reported genetic causes for LQTS is required. Methods: Utilizing an evidence-based framework, 3 gene curation teams blinded to each other’s work scored the level of evidence for 17 genes reported to cause LQTS. A Clinical Domain Channelopathy Working Group provided a final classification of these genes for causation of LQTS after assessment of the evidence scored by the independent curation teams. Results: Of 17 genes reported as being causative for LQTS, 9 ( AKAP9, ANK2, CAV3, KCNE1, KCNE2, KCNJ2, KCNJ5, SCN4B, SNTA1 ) were classified as having limited or disputed evidence as LQTS-causative genes. Only 3 genes ( KCNQ1, KCNH2, SCN5A ) were curated as definitive genes for typical LQTS. Another 4 genes ( CALM1, CALM2, CALM3, TRDN ) were found to have strong or definitive evidence for causality in LQTS with atypical features, including neonatal atrioventricular block. The remaining gene ( CACNA1C ) had moderate level evidence for causing LQTS. Conclusions: More than half of the genes reported as causing LQTS have limited or disputed evidence to support their disease causation. Genetic variants in these genes should not be used for clinical decision-making, unless accompanied by new and sufficient genetic evidence. The findings of insufficient evidence to support gene-disease associations may extend to other disciplines of medicine and warrants a contemporary evidence-based evaluation for previously reported disease-causing genes to ensure their appropriate use in precision medicine.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Reference50 articles.

1. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death

2. [Rare cardiac arrythmias of the pediatric age. II. Syncopal attacks due to paroxysmal ventricular fibrillation. (Presentation of 1st case in Italian pediatric literature)].;Romano C;Clin Pediatr (Bologna),1963

3. A new familial cardiac syndrome in children.;Ward OC;J Ir Med Assoc,1964

4. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome

5. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome

Cited by 277 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Detection of distant relatedness in biobanks to identify undiagnosed cases of Mendelian disease as applied to Long QT syndrome;Nature Communications;2024-08-29

2. Multimodal fusion learning for long QT syndrome pathogenic genotypes in a racially diverse population;npj Digital Medicine;2024-08-24

3. Generating Clinical-Grade Gene–Disease Validity Classifications Through the ClinGen Data Platforms;Annual Review of Biomedical Data Science;2024-08-23

4. What an anesthesiologist should know about pediatric arrhythmias;Pediatric Anesthesia;2024-08-15

5. High-Risk Nonclassical Long-QT Syndrome Genotypes: Spectrum of Genetic and Phenotypic Features;Circulation: Genomic and Precision Medicine;2024-08