دورية أكاديمية
Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.
| العنوان: | Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease. |
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| المؤلفون: | Silva SME; GEDORAC/DCC/SBC-Study Group on Rare Diseases with Cardiac Impairment from Brazilian Society of Cardiology, Hospital de Base do Distrito Federal (HBDF), Brasilia, Brazil., Chaves AVF; Cardiology Department, Hospital Agamenon Magalhães, Recife, Brazil.; RARUS, Referral Service for Rare Disease, Recife, Brazil.; Medicine Department, Mauricio de Nassau University Center UNINASSAU, Recife, Brazil., Antunes M; The Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.; Cardiology Department, São Francisco University (USF), Bragança Paulista, São Paulo, Brazil., Costabel JP; Coronary Care Unit, Cardiovascular Institute of Buenos Aires, Buenos Aires, Argentina., da Fonseca AA; DLE Laboratory, Institute Hermes Pardini S.A., Rio de Janeiro, Brazil., Furtado A; Sanofi, Global Medical Affairs-Rare Disease, Sao Paulo, Brazil., Gomez-Mesa JE; Cardiology Department, Hospital Fundacion Valle del Lili, Cali, Colombia.; Medicine Department, Icesi University, Cali, Colombia., Gutiérrez FJM; Mexican Social Security Institute, General Hospital of Zona 1, San Luis Potosi, Mexico., Caspi O; Heart Failure Unit, Cardiology Department, Rambam Health Care Campus and the B. Rapport Faculty of Medicine, Technion, Israel., Maksimova I; Sanofi, Global Medical Affairs-Rare Disease, Moscow, Russia., Maski M; Sanofi, Global Medical Affairs-Rare Disease, Cambridge, MA, USA., Micheletti C; DLE Laboratory, Institute Hermes Pardini S.A., São Paulo, Brazil., Pena JLB; Faculty of Medical Sciences of Minas Gerais, Belo Horizonte, MG, Brazil.; Echocardiography Department, Hospital Felício Rocho, Belo Horizonte, MG, Brazil., Ribeiro MG; DLE Laboratory, Fleury Group, Rio de Janeiro, Brazil., Rodríguez-González MJ; Heart Failure Department, Cardioinfantil Foundation, Cardiac Institute, Bogota, Colombia., Tufekcioglu O; Department of Cardiology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey., Onay H; Multigen Genetic Diseases Diagnosis Center, Izmir, Turkey.; Gene2Info Health Informatics, Istanbul, Turkey. |
| المصدر: | Cardiovascular diagnosis and therapy [Cardiovasc Diagn Ther] 2024 Apr 30; Vol. 14 (2), pp. 294-303. Date of Electronic Publication: 2024 Mar 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: AME Publishing Company Country of Publication: China NLM ID: 101601613 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2223-3652 (Print) Linking ISSN: 22233652 NLM ISO Abbreviation: Cardiovasc Diagn Ther Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Publication: SHEUNG WAN, Hong Kong : AME Publishing Company Original Publication: Hangzhou, China : CDT Office, [2011]- |
| مستخلص: | Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. Methods: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Results: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. Conclusions: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA ( TTR variants) and FD ( GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-23-191/coif). All authors report this study was funded by Sanofi. S.M.e.S. received speaker honoraria and grant/research support from Takeda, Pint Pharma, Pfizer and Sanofi; consulting fees from Chiesi Farmaceutici; and support for attending meetings and traveling from Takeda, Pint Pharma, Pfizer and Sanofi; and received support from Sanofi for current research and manuscript. A.V.F.C. received advisory fees and honoraria for lectures from Takeda, Sanofi and Pint-Pharma; support for attending meetings and/or traveling from Sanofi, Takeda and Pint-Pharma; and grant/research support from Multicare; Participation on a Data Safety Monitoring Board or Advisory Board for Takeda, Sanofi, and Pint-Pharma; and received support from Sanofi for current research and manuscript. M.A. received speaker honoraria from Takeda, Pfizer, and Sanofi; and grant/research support from Novartis and Pfizer; and received support from Sanofi for current research and manuscript. J.P.C. received support from Sanofi for current research and manuscript. A.A.d.F. received support from Sanofi for current research and manuscript. A.F. is an employee and shareholder of Sanofi and received support from Sanofi for current research and manuscript. J.E.G.M. received support from Sanofi for current research and manuscript. F.J.M.G. received support from Sanofi for current research and manuscript. O.C. received advisory fees from Sanofi Aventis and received support from Sanofi for current research and manuscript. I.M. is an employee and shareholder of Sanofi and received support from Sanofi for current research and manuscript. M.M. is an employee and shareholder of Sanofi and received support from Sanofi for current research and manuscript. C.M. received support from Sanofi for current research and manuscript. J.L.B.P. received advisory fees from Sanofi and received support from Sanofi for current research and manuscript. M.G.R. received support from Sanofi for current research and manuscript. M.J.R.G. received advisory fees and honoraria for lectures from Sanofi and received support from Sanofi for current research and manuscript. O.T. receives honoraria and lecture fees from Pfizer and Sanofi, payment for expert testimony from Pfizer; and received support from Sanofi for current research and manuscript. H.O. received speaker honoraria from Sanofi and received support from Sanofi for current research and manuscript. The authors have no other conflicts of interest to declare. (2024 Cardiovascular Diagnosis and Therapy. All rights reserved.) |
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| فهرسة مساهمة: | Keywords: Fabry disease (FD); hypertrophic cardiomyopathy (HCM); next-generation sequencing (NGS); transthyretin cardiac amyloidosis (ATTR-CA) |
| تواريخ الأحداث: | Date Created: 20240508 Latest Revision: 20240509 |
| رمز التحديث: | 20240509 |
| مُعرف محوري في PubMed: | PMC11070997 |
| DOI: | 10.21037/cdt-23-191 |
| PMID: | 38716318 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2223-3652 |
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| DOI: | 10.21037/cdt-23-191 |