2021年11月3日 · Heterozygous variants in TTN that are predicted to lead to truncated titin proteins (TTN -truncating variants or TTNtvs) can be found in 10 to 20% of patients with …

2024年1月16日 · Truncated mutants of titin are structurally incorporated in the sarcomere and cause axial disintegration, thereby leading to the pathogenesis of dilated cardiomyopathy. Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM).

2021年11月3日 · Heterozygous truncating variants in TTN (TTNtv), the gene coding for titin, cause dilated cardiomyopathy (DCM), but the underlying pathomechanisms are unclear and disease management remains uncerta...

2020年11月15日 · In all 6 individuals, a pathogenic or likely pathogenic variant was identified in TTN, confirming a genetic cause for their cardiomyopathy. If a variant of uncertain significance was identified, these are listed in Table 1C as well.

2021年8月31日 · Next-generation sequencing of clinical cohorts has revealed that heterozygous loss-of-function variants in titin (TTN), the largest human protein, are the leading genetic cause of idiopathic DCM (Figure 1A). 1, 6–8 TTN truncating variants (TTNtv), which include nonsense, frameshift, splicing, and copy number variants that damage the structure ...

2025年2月17日 · We identified a transcriptional enhancer of the essential sarcomere gene titin (TTN), which plays a critical role in TTN expression, sarcomere formation, and cardiomyocyte contractility. Heterozygous truncating variants in the sarcomere protein titin (TTN) are the most common genetic cause of heart failure.

2023年11月9日 · Two reports in this issue of the JCI shed light on a potential mechanism involving truncated TTN sarcomere integration and the potential for disruption of sarcomere structural integrity. Kellermayer, Tordai, and colleagues confirmed the presence of truncated TTN protein in human DCM samples.

2021年12月14日 · Cardiomyocyte genome editing using SpCas9 and a TTNtv-specific guide RNA restored the TTN protein reading frame, which increased full-length TTN protein levels, reduced TTN truncation peptides, and increased sarcomere function in cardiac microtissue assays.

Titin (TTN) is the largest protein in humans, and TTN truncating variants (TTNtv; SNPs that lead to premature stop codons, indels that cause frameshifts in the coding sequence and variants that disrupt canonical splice sites) have recently been shown to be the leading genetic cause of Dilated Cardiomyopathy (DCM), present in up to 25% of cases ...

2021年11月3日 · Heterozygous truncating variants in TTN (TTNtv), the gene coding for titin, cause dilated cardiomyopathy (DCM), but the underlying pathomechanisms are unclear and disease management remains uncertain.