1 research outputs found
A Novel Nonsense Pathogenic TTN Variant Identified in a Patient with Severe Dilated Cardiomyopathy
Both genetic and environmental factors contribute to the development of dilated
cardiomyopathy. Among the genes involved, TTN mutations, including truncated variants, explain
25% of DCM cases. We performed genetic counseling and analysis on a 57-year-old woman
diagnosed with severe DCM and presenting relevant acquired risk factors for DCM (hypertension,
diabetes, smoking habit, and/or previous alcohol and cocaine abuse) and with a family history of
both DCM and sudden cardiac death. The left ventricular systolic function, as assessed by
standard echocardiography, was 20%. The genetic analysis performed using TruSight Cardio
panel, including 174 genes related to cardiac genetic diseases, revealed a novel nonsense TTN
variant (TTN:c.103591A > T, p.Lys34531*), falling within the M-band region of the titin protein. This
region is known for its important role in maintaining the structure of the sarcomere and in
promoting sarcomerogenesis. The identified variant was classified as likely pathogenic based on
ACMG criteria. The current results support the need of genetic analysis in the presence of a family
history, even when relevant acquired risk factors for DCM may have contributed to the severity of
the disease