4.8 Article

Truncated titin proteins and titin haploinsufficiency are targets for functional recovery in human cardiomyopathy due to TTN mutations

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Summary: Truncated titin proteins were quantitatively detected in human DCM hearts with TTNtvs, while full-length titin was reduced in TTNtvs(+) DCM hearts. Disease severity did not correlate with TTNtv location, and transcriptomic profiling showed few differences between TTNtv(+) and TTNtv(-) DCM hearts. Contractility in isolated human adult cardiomyocytes from TTNtv(+) DCM hearts did not show defects compared to TTNtv(-) hearts, supporting a combined dominant-negative and haploinsufficiency mechanism in disease.

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