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

• DOI: 10.1161/circgen.123.004404
• Publication Date: 2024-02-14T10:00:22Z
• Authors: Almudena Amor-Sal...; Alfredo Santana R...; Hazhee Rasoul; José F. Rodríguez...; Oana Moldovan; Thomas Morris Hey; María Gallego Del...; David López Cuenca; Daniel de Castro ...; María Teresa Basu...; Rosa Macías-Ruiz; María Eugenia Fue...; Joseph Galvin; Raquel Bilbao Que...; Luis de la Higuer...; Juan Pablo Trujil...; Loida María Garcí...; Ivonne Cárdenas-R...; Juan Jiménez-Jáimez; Soledad García-He...; María Valverde-Gómez; Iria Gómez-Díaz; Javier Limeres Fr...; José M. García-Pi...; Juan R. Gimeno-Bl...; Konstantinos Sava...; Pablo García-Pavía; Juan Pablo Ochoa
• Keywords: Left ventricular noncompaction; Dilated Cardiomyopathy

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