Investigating TNNC1 gene inheritance and clinical outcomes through a comprehensive familial study

Abstract Hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) have significant phenotypic overlap and a similar genetic background, both caused mainly by variants in sarcomeric genes. HCM is the most common cardiomyopathy, while RCM is a rare and often underdiagnosed heart condition, with a poor prognosis. This study focuses on a large family with four infants diagnosed with fatal RCM associated with biventricular hypertrophy. Affected infants were found to be homozygous for NM_003280.3( TNNC1 ):c.23C>T(p.Ala8Val) variant. Interestingly, this variant resulted in a low penetrance and mild form of hypertrophic cardiomyopathy (HCM) in relatives carrying a single copy of the variant. Overall, this study underscores the complex nature of genetic inheritance in cardiomyopathies and the wide range of clinical presentations they can exhibit. This emphasizes the vital role of genetic testing in providing essential insights crucial for diagnosis, prognosis, early intervention, and the development of potential treatment strategies.