Mutation location of HCM-causing troponin T mutations defines the degree of myofilament dysfunction in human cardiomyocytes.

ABSTRACT:

Background

The clinical outcome of hypertrophic cardiomyopathy patients is not only determined by the disease-causing mutation but influenced by a variety of disease modifiers. Here, we defined the role of the mutation location and the mutant protein dose of the troponin T mutations I79N, R94C and R278C.

Methods and results

We determined myofilament function after troponin exchange in permeabilized single human cardiomyocytes as well as in cardiac patient samples harboring the R278C mutation. Notably, we found that a small dose of mutant protein is sufficient for the maximal effect on myofilament Ca²⁺-sensitivity for the I79N and R94C mutation while the mutation location determines the magnitude of this effect. While incorporation of I79N and R94C increased myofil

SUBMITTER: Schuldt M 

PROVIDER: S-EPMC10616699 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature