Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction
This study explored a gene called TBX20 and its connection to two heart conditions: dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC). These are diseases where the heart becomes enlarged or has a spongy, underdeveloped structure, making it harder to pump blood efficiently. DCM and LVNC can lead to heart failure or dangerous irregular heart rhythms.
Scientists already knew that genes play a role in many heart diseases, but in over half of the people with DCM or LVNC, no known genetic cause is found. TBX20 is a gene important for heart development in the womb and has been linked to some congenital heart defects (conditions present from birth in which the anatomy of the heart is not built correctly), but its role in DCM and LVNC hadn’t been clearly proven—until now.
In this large study, researchers looked at over 7,400 patients with DCM or LVNC and compared them with more than 146,000 people without these conditions. They discovered that people with so-called “truncating variants” in the TBX20 gene—mutations that disrupt the gene’s function—were far more likely to have DCM or LVNC. This strong association was also seen in families, where these mutations tended to be inherited along with the disease.
The study followed 57 individuals with TBX20 mutations. Over 70% developed DCM or LVNC, and one-third of those also had congenital heart defects. While some patients experienced symptoms like shortness of breath or dizziness, about 40% had no symptoms when diagnosed. The disease generally appeared earlier in life for those with additional congenital heart defects.
Importantly, although TBX20 mutations increased the risk of developing DCM or LVNC, the overall disease course was relatively mild. Only a small number of patients had life-threatening arrhythmias or needed heart transplants, and these severe outcomes mostly affected those diagnosed very young and who also had birth defects.
The findings support including TBX20 in genetic testing for patients with DCM or LVNC, especially when the heart has a spongy or underdeveloped appearance, or when congenital heart defects are also present. This could help identify at-risk family members earlier and guide follow-up and care.
In short, this research adds a crucial piece to the puzzle of inherited heart disease and opens the door to better diagnosis and prevention for affected families.
Amor-Salamanca A, Santana Rodríguez A, Rasoul H, Rodríguez-Palomares JF, Moldovan O, Hey TM, Delgado MG, Cuenca DL, de Castro Campos D, Basurte-Elorz MT, Macías-Ruiz R, Fuentes Cañamero ME, Galvin J, Bilbao Quesada R, de la Higuera Romero L,Trujillo-Quintero JP, García-Cruz LM, Cárdenas-Reyes I, Jiménez-Jáimez J, García-Hernández S, Valverde-Gómez M, Gómez-Díaz I, Limeres Freire J, García-Pinilla JM, Gimeno-Blanes JR, Savattis K, García-Pavía P, Ochoa JP. Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction. Circ Genom Precis Med.2024 Feb14:e004404. doi:10.1161/CIRCGEN.123.004404. Epub ahead of print. PMID:38353104
Prepared by Pablo García Pavía, Fernando Dominguez and Ruth Biller