Expanding the TTN mutation spectrum for dilated cardiomyopathy diagnosis

Announcing a new article publication for Cardiovascular Innovations and Applications journal. Dilated cardiomyopathy (DCM), a severe heart disease, is the leading cause of heart failure and sudden cardiac death worldwide. DCM is defined by a dilated and deficient systolic left ventricle (LV) and is a major risk factor for morbidity and mortality worldwide. DCM progression can be ascribed to genetic and non-genetic factors, including hypertension, infectious agents, toxins, and drugs.

Sarcomere genes play crucial roles in myocardial cells' physical structure and physiological function. Various cardiomyopathies can be attributed to variations in sarcomere genes. TTN, the largest protein in the human body, is important in sarcomere structure and function; variations in the TTN gene are associated with many hereditary cardiomyopathies, including DCM, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, catecholamine-induced polymorphic ventricular tachycardia, and left ventricular non-compaction.

Through a combination of whole-exome sequencing and filtering of cardiomyopathy-associated genes, the authors of this article identified a novel splicing variant (c.35485+1G>A), a novel frameshift deletion variant (c.82137del: p.A27380Lfs*3), and a novel frameshift insertion variant (c.80415insA: p. V26806Sfs*3) in TTN as possible causative genes of DCM in three Chinese patients. The study broadens the spectrum of TTN variants and may help with genetic screening for related diseases. This study supplements the TTN gene mutation library and improves genetic diagnosis strategies for DCM. Additional functional studies of the TTN protein with these variants are recommended, and may contribute to ascertaining the molecular and pathological mechanisms of DCM.