This is an update as of June 2025 on the research project funded by Silvey Family Foundation and Team Titin. This research is being conducted by Jennifer Roggenbuck, MS, CGC, Professor of Neurology at The Ohio State University Wexner Medical Center, along with collaborators at The University of Arizona.
“Harmful changes in the TTN gene (known as TTNtv), the gene encoding the giant muscle protein, titin, are the leading genetic cause of dilated cardiomyopathy. TTN-related dilated cardiomyopathy is inherited in families, though not all persons with the genetic change will develop cardiomyopathy. Currently, it is not understood why some persons with harmful changes in TTN develop serious symptoms, while others do not. One clue is that affected persons seem to have an abnormal, shortened version of the titin protein made from the abnormal gene that has a toxic effect in heart tissue. The titin protein is also present in the skeletal muscle (the muscle of the body) and we have found that a subset of persons with single harmful genetic changes in TTN gene also have a mild form of muscular dystrophy or myopathy.
Our previous work has shown that the skeletal muscle may be somewhat protected from the harmful effects of TTNtv because the genetic recipe made from the TTN gene (known as RNA) is broken down by the body before a toxic shortened protein can be produced (a process known as nonsense-mediated decay). We are currently investigating whether nonsense mediated decay efficiency correlates with disease severity in persons with TTNtv. If we identify a protective effect of nonsense mediated decay, abnormal TTN RNA may be a therapeutic target to prevent the formation of toxic protein which is so damaging to heart function. For more about our work, see our recent publication, Pathomechanisms of Monoallelic variants in TTN causing skeletal muscle disease.”
