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Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction.
Amor-Salamanca, Almudena; Santana Rodríguez, Alfredo; Rasoul, Hazhee; Rodríguez-Palomares, José F; Moldovan, Oana; Hey, Thomas Morris; Delgado, María Gallego; Cuenca, David López; de Castro Campos, Daniel; Basurte-Elorz, María Teresa; Macías-Ruiz, Rosa; Fuentes Cañamero, María Eugenia; Galvin, Joseph; Bilbao Quesada, Raquel; de la Higuera Romero, Luis; Trujillo-Quintero, Juan Pablo; García-Cruz, Loida María; Cárdenas-Reyes, Ivonne; Jiménez-Jáimez, Juan; García-Hernández, Soledad; Valverde-Gómez, María; Gómez-Díaz, Iria; Limeres Freire, Javier; García-Pinilla, José M; Gimeno-Blanes, Juan R; Savattis, Konstantinos; García-Pavía, Pablo; Ochoa, Juan Pablo.
Afiliação
  • Amor-Salamanca A; 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.).
  • Santana Rodríguez A; Clinical Genetics Unit, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.).
  • Rasoul H; Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.).
  • Rodríguez-Palomares JF; Inherited Cardiovascular Diseases Unit, St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom (H.R., K.S.).
  • Moldovan O; Cardiovascular Imaging Unit and Inherited Cardiac Diseases Unit, Cardiology Department, Vall d'Hebron University Hospital, Barcelona, Spain (J.F.R.-P., J.L.F.).
  • Hey TM; Vall d'Hebron Rsrch Unit, Barcelona, Spain (J.F.R.-P.).
  • Delgado MG; Universitat Autònoma Barcelona, Spain (J.F.R.-P., J.P.T.-Q.).
  • Cuenca DL; 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.).
  • de Castro Campos D; 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.).
  • Basurte-Elorz MT; Serviço de Genética Médica, Department de Pediatria, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Portugal (O.M.).
  • Macías-Ruiz R; Department of Cardiology, The Clinic of Inherited Cardiovascular Diseases, Odense University Hospital, Denmark (T.M.H.).
  • Fuentes Cañamero ME; 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.).
  • Galvin J; Cardiology Department, Hospital Universitario de Salamanca, Spain (M.G.D.).
  • Bilbao Quesada R; Biomedical Research Institute of Salamanca, Gerencia Regional de Salud de Castilla y León, Spain (M.G.D.).
  • de la Higuera Romero L; Department of Cardiology, Inherited Cardiac Diseases Unit, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain (D.L.C., J.R.G.-B.).
  • Trujillo-Quintero JP; 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.).
  • García-Cruz LM; Department of Cardiology, Complejo Hospitalario de Navarra, Pamplona, Spain (M.T.B.-E.).
  • Cárdenas-Reyes I; Cardiology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain (R.M.-R., J.J.-J.).
  • Jiménez-Jáimez J; Instituto de Investigación Biosanitaria Instituto de Investigación Biosanitaria de Granada (IBS-GRANADA), Spain (R.M.-R., J.J.-J.).
  • García-Hernández S; Cardiology Department, Hospital Universitario de Badajoz, Spain (M.E.F.C.).
  • Valverde-Gómez M; Department of Cardiology, University College Dublin School of Medicine, Mater Misericordiae University Hospital, Ireland (J.G.).
  • Gómez-Díaz I; Cardiology Department, Hospital Álvaro Cunqueiro, Vigo, Spain (R.B.Q.).
  • Limeres Freire J; 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.).
  • García-Pinilla JM; Universitat Autònoma Barcelona, Spain (J.F.R.-P., J.P.T.-Q.).
  • Gimeno-Blanes JR; Center for Genomic Medicine, Parc Taulí Hospital Universitari, Sabadell, Spain (J.P.T.-Q.).
  • Savattis K; Institut d'Investigació i Innovació Parc Taulí, Sabadell, Spain (J.P.T.-Q.).
  • García-Pavía P; Clinical Genetics Unit, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.).
  • Ochoa JP; Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Spain (A.S.R., L.M.G.-C.).
Circ Genom Precis Med ; 17(2): e004404, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38353104
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, 25-753.6-14.5) 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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Cardiomiopatia Dilatada / Cardiopatias Congênitas Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Circ Genom Precis Med Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Cardiomiopatia Dilatada / Cardiopatias Congênitas Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Circ Genom Precis Med Ano de publicação: 2024 Tipo de documento: Article