Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction
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.
| Errataetall: |
CommentIn: Circ Genom Precis Med. 2024 Apr;17(2):e004598. - PMID 38497209 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
Circulation. Genomic and precision medicine - 17(2024), 2 vom: 28. Apr., Seite e004404 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 18.04.2024 Date Revised 18.04.2024 published: Print-Electronic CommentIn: Circ Genom Precis Med. 2024 Apr;17(2):e004598. - PMID 38497209 Citation Status MEDLINE |
|---|
| doi: |
10.1161/CIRCGEN.123.004404 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368432114 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368432114 | ||
| 003 | DE-627 | ||
| 005 | 20240418232558.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240214s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/CIRCGEN.123.004404 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1379.xml |
| 035 | |a (DE-627)NLM368432114 | ||
| 035 | |a (NLM)38353104 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Amor-Salamanca, Almudena |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.04.2024 | ||
| 500 | |a Date Revised 18.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Circ Genom Precis Med. 2024 Apr;17(2):e004598. - PMID 38497209 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cardiomyopathies | |
| 650 | 4 | |a cardiomyopathy, dilated | |
| 650 | 4 | |a heart defects, congenital | |
| 650 | 4 | |a heart ventricles | |
| 650 | 4 | |a high-throughput nucleotide sequencing | |
| 650 | 4 | |a human genetics | |
| 650 | 4 | |a transcription factors | |
| 650 | 7 | |a TBX20 protein, human |2 NLM | |
| 650 | 7 | |a T-Box Domain Proteins |2 NLM | |
| 700 | 1 | |a Santana Rodríguez, Alfredo |e verfasserin |4 aut | |
| 700 | 1 | |a Rasoul, Hazhee |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Palomares, José F |e verfasserin |4 aut | |
| 700 | 1 | |a Moldovan, Oana |e verfasserin |4 aut | |
| 700 | 1 | |a Hey, Thomas Morris |e verfasserin |4 aut | |
| 700 | 1 | |a Delgado, María Gallego |e verfasserin |4 aut | |
| 700 | 1 | |a Cuenca, David López |e verfasserin |4 aut | |
| 700 | 1 | |a de Castro Campos, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Basurte-Elorz, María Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Macías-Ruiz, Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Fuentes Cañamero, María Eugenia |e verfasserin |4 aut | |
| 700 | 1 | |a Galvin, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Bilbao Quesada, Raquel |e verfasserin |4 aut | |
| 700 | 1 | |a de la Higuera Romero, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Trujillo-Quintero, Juan Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a García-Cruz, Loida María |e verfasserin |4 aut | |
| 700 | 1 | |a Cárdenas-Reyes, Ivonne |e verfasserin |4 aut | |
| 700 | 1 | |a Jiménez-Jáimez, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a García-Hernández, Soledad |e verfasserin |4 aut | |
| 700 | 1 | |a Valverde-Gómez, María |e verfasserin |4 aut | |
| 700 | 1 | |a Gómez-Díaz, Iria |e verfasserin |4 aut | |
| 700 | 1 | |a Limeres Freire, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a García-Pinilla, José M |e verfasserin |4 aut | |
| 700 | 1 | |a Gimeno-Blanes, Juan R |e verfasserin |4 aut | |
| 700 | 1 | |a Savattis, Konstantinos |e verfasserin |4 aut | |
| 700 | 1 | |a García-Pavía, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Ochoa, Juan Pablo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Circulation. Genomic and precision medicine |d 2018 |g 17(2024), 2 vom: 28. Apr., Seite e004404 |w (DE-627)NLM280989210 |x 2574-8300 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2024 |g number:2 |g day:28 |g month:04 |g pages:e004404 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1161/CIRCGEN.123.004404 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 17 |j 2024 |e 2 |b 28 |c 04 |h e004404 | ||