Prevalence of TTN mutations in patients with dilated cardiomyopathy

Fang, Huijuan; Liu, Bao-Peng

doi:10.1007/s00059-019-4825-4

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…According to Fatkin et al the prevalence of TTN tv is 20% among individuals with DCM, whereas only 0.5% of the general population carries this type of mutation 83 , 84 . The aforementioned data aligns with the results of Fang et al 85 survey, which indicated an overall prevalence rate of 17%. The survey also revealed that 23% of cases were familial, while 16% were sporadic.…”

Section: Resultssupporting

confidence: 90%

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies

Jolfayi,

Kohansal,

Ghasemi

et al. 2024

Sci Rep

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The giant protein titin (TTN) is a sarcomeric protein that forms the myofibrillar backbone for the components of the contractile machinery which plays a crucial role in muscle disorders and cardiomyopathies. Diagnosing TTN pathogenic variants has important implications for patient management and genetic counseling. Genetic testing for TTN variants can help identify individuals at risk for developing cardiomyopathies, allowing for early intervention and personalized treatment strategies. Furthermore, identifying TTN variants can inform prognosis and guide therapeutic decisions. Deciphering the intricate genotype–phenotype correlations between TTN variants and their pathologic traits in cardiomyopathies is imperative for gene-based diagnosis, risk assessment, and personalized clinical management. With the increasing use of next-generation sequencing (NGS), a high number of variants in the TTN gene have been detected in patients with cardiomyopathies. However, not all TTN variants detected in cardiomyopathy cohorts can be assumed to be disease-causing. The interpretation of TTN variants remains challenging due to high background population variation. This narrative review aimed to comprehensively summarize current evidence on TTN variants identified in published cardiomyopathy studies and determine which specific variants are likely pathogenic contributors to cardiomyopathy development.

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Section: Resultssupporting

confidence: 90%

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies

Jolfayi,

Kohansal,

Ghasemi

et al. 2024

Sci Rep

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“…(49) TTN truncating variants are a common cause of dilated cardiomyopathy, occurring in approximately 25% of genetic dilated cardiomyopathy and in 18% of sporadic cases. (50,51) In our patients with IVA, although no structural heart disease had been identi ed, this did not exclude the possibility that these patients would eventually develop cardiomyopathy. It is also possible that arrhythmia precedes structural changes, and the patients may later manifest structural change in the heart.…”

Section: Discussionmentioning

confidence: 90%

Identification of Genetic Variants in Patients with Idiopathic Ventricular Arrhythmia by Taiwan Arrhythmia Gene Panel Implying Underlying Mechanisms

Chen,

Chang,

Chiu

et al. 2024

Preprint

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Background Sudden cardiac death (SCD) due to idiopathic ventricular tachycardia or ventricular fibrillation is a catastrophic disease. Its genetic basis is heterogeneous and has been rarely addressed in Asia. We aim to find variants in an Asian cohort of idiopathic ventricular arrhythmia (IVA). Methods Nationwide patients with IVA were consecutively recruited. We designed a SCD gene panel (134 genes) to detect variants by next-generation sequencing (NGS) including most of the channelopathy and cardiomyopathy genes. Results A total of 40 IVA patients were included. Thirteen variants with unknown significance (VUS) and 7 pathogenic/likely pathogenic (P/LP) variants were identified in 20 patients (50%). All variants were novel and not found in dbSNP, ExAC and our general population. The identified variants were in genes implicated for long QT or Brugada syndromes (SCN5A, KCNH2, CACNA1C and ANK2), cardiomyopathy (MYH6, DSP and TTN) and catecholaminergic polymorphic ventricular tachycardia (RYR2). Patients with P/LP were younger, and more were women than those with VUS. Conclusions A high yield rate of genetic test was found in the largest NGS cohort of Asian IVA patients. These patients should be vigorously followed up for possible channelopathy or cardiomyopathy with repeated provocative test and myocardial imaging.

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“…Mutations of TTN are the most common cause of genetic cardiomyopathy and account for 20–25% of genetic DCM [ 11 ]. TTNtv are associated with a later presentation (47.9 years) and greater longevity (70.4 years) compared to other genetic and non-genetic causes of cardiomyopathy [ 24 , 44 ]. While patients with TTNtv often present later in life, there is evidence that carriers have pre-symptomatic cardiac dysfunction with eccentric cardiac remodeling as detected by MRI [ 35 ].…”

Section: Truncation Mutations In Ttn Cause Dilamentioning

confidence: 99%

Modifications of Titin Contribute to the Progression of Cardiomyopathy and Represent a Therapeutic Target for Treatment of Heart Failure

Tharp

Mestroni

Taylor

2020

JCM

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Titin is the largest human protein and an essential component of the cardiac sarcomere. With multiple immunoglobulin(Ig)-like domains that serve as molecular springs, titin contributes significantly to the passive tension, systolic function, and diastolic function of the heart. Mutations leading to early termination of titin are the most common genetic cause of dilated cardiomyopathy. Modifications of titin, which change protein length, and relative stiffness affect resting tension of the ventricle and are associated with acquired forms of heart failure. Transcriptional and post-translational changes that increase titin’s length and extensibility, making the sarcomere longer and softer, are associated with systolic dysfunction and left ventricular dilation. Modifications of titin that decrease its length and extensibility, making the sarcomere shorter and stiffer, are associated with diastolic dysfunction in animal models. There has been significant progress in understanding the mechanisms by which titin is modified. As molecular pathways that modify titin’s mechanical properties are elucidated, they represent therapeutic targets for treatment of both systolic and diastolic dysfunction. In this article, we review titin’s contribution to normal cardiac physiology, the pathophysiology of titin truncation variations leading to dilated cardiomyopathy, and transcriptional and post-translational modifications of titin. Emphasis is on how modification of titin can be utilized as a therapeutic target for treatment of heart failure.

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Prevalence of TTN mutations in patients with dilated cardiomyopathy

Cited by 8 publications

References 32 publications

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies

Identification of Genetic Variants in Patients with Idiopathic Ventricular Arrhythmia by Taiwan Arrhythmia Gene Panel Implying Underlying Mechanisms

Modifications of Titin Contribute to the Progression of Cardiomyopathy and Represent a Therapeutic Target for Treatment of Heart Failure

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