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Review
. 2022 Sep;24(9):1069-1075.
doi: 10.1007/s11886-022-01726-0. Epub 2022 Jun 27.

Titin-related Cardiomyopathy: Is it a Distinct Disease?

Celine F Santiago  1   2 , Inken G Huttner  1   2 , Diane Fatkin  3   4   5
Affiliations
Review

Titin-related Cardiomyopathy: Is it a Distinct Disease?

Celine F Santiago et al. Curr Cardiol Rep. 2022 Sep.

Abstract

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. 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.

Keywords: Dilated cardiomyopathy; Disease mechanisms; Personalised medicine; Titin truncation.

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References

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