Titin-related cardiomyopathy: is it a distinct disease?
CF Santiago, IG Huttner, D Fatkin - Current Cardiology Reports, 2022 - Springer
CF Santiago, IG Huttner, D Fatkin
Current Cardiology Reports, 2022•SpringerAbstract Purpose of Review Truncating TTN variants (TTN tv) are the most common genetic
cause of dilated cardiomyopathy (DCM), but the underlying mechanisms are incompletely
understood and effective therapeutic strategies are lacking. Here we review recent data that
shed new light on the functional consequences of TTN tv and how these effects may vary
with mutation location. Recent Findings Whether TTN tv act by haploinsufficiency or
dominant negative effects has been hotly debated. New evidence now implicates both …
cause of dilated cardiomyopathy (DCM), but the underlying mechanisms are incompletely
understood and effective therapeutic strategies are lacking. Here we review recent data that
shed new light on the functional consequences of TTN tv and how these effects may vary
with mutation location. Recent Findings Whether TTN tv act by haploinsufficiency or
dominant negative effects has been hotly debated. New evidence now implicates both …
Purpose of Review
Truncating TTN variants (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM), but the underlying mechanisms are incompletely understood and effective therapeutic strategies are lacking. Here we review recent data that shed new light on the functional consequences of TTNtv and how these effects may vary with mutation location.
Recent Findings
Whether TTNtv act by haploinsufficiency or dominant negative effects has been hotly debated. New evidence now implicates both mechanisms in TTNtv-related DCM, showing reduced titin content and persistent truncated titin that may be incorporated into protein aggregates. The extent to which aggregate formation and protein quality control defects differ with TTNtv location and contribute to contractile dysfunction is unresolved.
Summary
TTNtv-associated DCM has a complex etiology that involves varying combinations of wild-type titin deficiency and dominant negative effects of truncated mutant titin. Therapeutic strategies to improve protein handling may be beneficial in some cases.
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