Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction
Amor-Salamanca, Almudena (Health in Code SL)
Santana Rodríguez, Alfredo (Universidad de Las Palmas de Gran Canaria)
Rasoul, Hazhee (St. Bartholomew's Hospital)
Rodríguez-Palomares, José F. (Hospital Universitari Vall d'Hebron)
Moldovan, Oana (Centro Hospitalar Universitário Lisboa Norte)
Hey, Thomas Morris (Odense University Hospital)
Gallego-Delgado, María (Instituto de Salud Carlos III)
Cuenca, David López (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
de Castro Campos, Daniel (Hospital Universitario Puerta de Hierro)
Basurte-Elorz, María Teresa (Complejo Hospitalario de Navarra)
Macías-Ruiz, Rosa (Instituto de Investigación Biosanitaria de Granada)
Fuentes Cañamero, María Eugenia (Hospital Universitario de Badajoz)
Galvin, Joseph (University College Dublin School of Medicine)
Bilbao Quesada, Raquel (Hospital Álvaro Cunqueiro (Vigo))
de la Higuera Romero, Luis (Health in Code SL)
Trujillo-Quintero, Juan Pablo (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
García-Cruz, Loida María (Universidad de Las Palmas de Gran Canaria)
Cárdenas-Reyes, Ivonne (Health in Code SL)
Jiménez-Jáimez, Juan (Hospital Universitario Virgen de las Nieves)
García-Hernández, Soledad (Hospital Universitario San Cecilio)
Valverde-Gómez, María (Hospital Universitario 12 de Octubre)
Gómez-Díaz, Iria (Health in Code SL)
Limeres Freire, Javier (Hospital Universitari Vall d'Hebron)
García-Pinilla, José Manuel (Universidad de Málaga)
Gimeno-Blanes, Juan R. (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Savattis, Konstantinos (Queen Mary University of London)
García-Pavía, Pablo (Centro Nacional de Investigaciones Cardiovasculares Carlos III (Madrid, Espanya))
Ochoa, Juan Pablo (Centro Nacional de Investigaciones Cardiovasculares Carlos III (Madrid, Espanya))
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	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. 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. 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. 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.
Grants:	Instituto de Salud Carlos III PI17/01941 Instituto de Salud Carlos III PI20/01379
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cardiomyopathies ; Cardiomyopathy, dilated ; Heart defects, congenital ; Heart ventricles ; High-throughput nucleotide sequencing ; Human genetics ; Transcription factors
Published in:	Circulation. Genomic and precision medicine, Vol. 17 (february 2024) , p. e004404, ISSN 2574-8300

DOI: 10.1161/CIRCGEN.123.004404
PMID: 38353104

11 p, 1022.6 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
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Articles > Published articles