Role of <i>TBX20</i> Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction-Reference-Cited by-同舟云学术

Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction

Published:2024-04 Issue:2 Volume:17 Page:
ISSN:2574-8300
Container-title:Circulation: Genomic and Precision Medicine
language:en
Short-container-title:Circ: Genomic and Precision Medicine

Author:

Amor-Salamanca Almudena¹^ORCID,Santana Rodríguez Alfredo²³,Rasoul Hazhee⁴^ORCID,Rodríguez-Palomares José F.⁵⁶⁷⁸⁹,Moldovan Oana¹⁰^ORCID,Hey Thomas Morris¹¹^ORCID,Delgado María Gallego⁸¹²¹³^ORCID,Cuenca David López¹⁴^ORCID,de Castro Campos Daniel¹⁵^ORCID,Basurte-Elorz María Teresa¹⁶^ORCID,Macías-Ruiz Rosa¹⁷¹⁸^ORCID,Fuentes Cañamero María Eugenia¹⁹^ORCID,Galvin Joseph²⁰^ORCID,Bilbao Quesada Raquel²¹^ORCID,de la Higuera Romero Luis¹,Trujillo-Quintero Juan Pablo⁷²²²³^ORCID,García-Cruz Loida María²³,Cárdenas-Reyes Ivonne¹,Jiménez-Jáimez Juan¹⁷¹⁸^ORCID,García-Hernández Soledad¹²⁴^ORCID,Valverde-Gómez María¹²⁵^ORCID,Gómez-Díaz Iria¹,Limeres Freire Javier⁵⁹,García-Pinilla José M.⁸²⁶²⁷^ORCID,Gimeno-Blanes Juan R.⁸⁹¹⁴^ORCID,Savattis Konstantinos⁴²⁸²⁹³⁰,García-Pavía Pablo⁸⁹¹⁵³¹³²^ORCID,Ochoa Juan Pablo¹¹⁵³²^ORCID

Affiliation:

1. Cardiology Department, Health in Code SL, A Coruña, Spain (A.A.-S., L.d.l.H.R., I.C.-R., S.G.-H., M.V.-G., I.G.-D., J.P.O.).

2. Clinical Genetics Unit, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.).

3. Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.).

4. Inherited Cardiovascular Diseases Unit, St. Bartholomew’s Hospital, Barts Health NHS Trust, London, United Kingdom (H.R., K.S.).

5. Cardiovascular Imaging Unit and Inherited Cardiac Diseases Unit, Cardiology Department, Vall d′Hebron University Hospital, Barcelona, Spain (J.F.R.-P., J.L.F.).

6. Vall d′Hebron Rsrch Unit, Barcelona, Spain (J.F.R.-P.).

7. Universitat Autònoma Barcelona, Spain (J.F.R.-P., J.P.T.-Q.).

8. Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain (J.F.R.-P., M.G.D., J.M.G.-P., J.R.G.-B., P.G.-P.).

9. European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, The Netherlands (J.F.R.-P., J.L.F., J.R.G.-B., P.G.-P.).

10. Serviço de Genética Médica, Department de Pediatria, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Portugal (O.M.).

11. Department of Cardiology, The Clinic of Inherited Cardiovascular Diseases, Odense University Hospital, Denmark (T.M.H.).

12. Cardiology Department, Hospital Universitario de Salamanca, Spain (M.G.D.).

13. Biomedical Research Institute of Salamanca, Gerencia Regional de Salud de Castilla y León, Spain (M.G.D.).

14. Department of Cardiology, Inherited Cardiac Diseases Unit, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain (D.L.C., J.R.G.-B.).

15. Department of Cardiology, Heart Failure and Inherited Cardiac Diseases Unit, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain (D.d.C.C., P.G.-P., J.P.O.).

16. Department of Cardiology, Complejo Hospitalario de Navarra, Pamplona, Spain (M.T.B.-E.).

17. Cardiology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain (R.M.-R., J.J.-J.).

18. Instituto de Investigación Biosanitaria Instituto de Investigación Biosanitaria de Granada (IBS-GRANADA), Spain (R.M.-R., J.J.-J.).

19. Cardiology Department, Hospital Universitario de Badajoz, Spain (M.E.F.C.).

20. Department of Cardiology, University College Dublin School of Medicine, Mater Misericordiae University Hospital, Ireland (J.G.).

21. Cardiology Department, Hospital Álvaro Cunqueiro, Vigo, Spain (R.B.Q.).

22. Center for Genomic Medicine, Parc Taulí Hospital Universitari, Sabadell, Spain (J.P.T.-Q.).

23. Institut d’Investigació i Innovació Parc Taulí, Sabadell, Spain (J.P.T.-Q.).

24. Inherited Cardiac Diseases Unit, Hospital Universitario San Cecilio, Granada, Spain (S.G.-H.).

25. Cardiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain (M.V.-G.).

26. Department of Cardiology, Heart Failure and Inherited Cardiac Diseases Unit, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain (J.M.G.-P.).

27. Department of Medicine and Dermatology, Universidad de Málaga, Spain (J.M.G.-P.).

28. Institute for Cardiovascular Science, University College London, United Kingdom (K.S.).

29. Biomedical Research Center, National Institute for Health and Care Research (NIHR) University College London Hospitals, United Kingdom (K.S.).

30. William Harvey Research Institute, Queen Mary University of London, United Kingdom (K.S.).

31. Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain (P.G.-P.).

32. Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (P.G.-P., J.P.O.).

Abstract

BACKGROUND: Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant ( TBX20tv ) and DCM/LVNC. METHODS: TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers. RESULTS: TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90–541.45; P <0.0001) and 99.76 (95% CI, 34.60–287.62; P <0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25–75:3.6–14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias. CONCLUSIONS: TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv -associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference33 articles.

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