Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Sequencing Study Links Mutations in Major Heart Muscle Protein to Development of Dilated Cardiomyopathy

By LabMedica International staff writers
Posted on 26 Jan 2015
Print article
Image: Illustration of a normal heart compared to a heart with dilated cardiomyopathy (Photo courtesy of Blausen Gallery 2014. Wikiversity Journal of Medicine).
Image: Illustration of a normal heart compared to a heart with dilated cardiomyopathy (Photo courtesy of Blausen Gallery 2014. Wikiversity Journal of Medicine).
British heart disease researchers using advanced gene sequencing techniques have identified mutations in the TTN gene, which encodes the muscle protein titin, linked to development of dilated cardiomyopathy (DCM) that are different from benign mutations in this gene that are carried by a large percentage of the population.

In DCM a portion of the myocardium is dilated, often without any obvious cause. Left or right ventricular systolic pump function of the heart is impaired, leading to progressive cardiac enlargement and hypertrophy, a process called remodeling. Dilated cardiomyopathy is the most common form of non-ischemic cardiomyopathy, and one in three cases of congestive heart failure (CHF) is due to dilated cardiomyopathy. It occurs more frequently in men than in women, and is most common between the ages of 20 and 60 years.

Titin, also known as connectin, is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed. With its length of from about 27,000 to 33,000 amino acids (depending on the splice isoform), titin is the largest known protein, and the TTN gene contains the largest number of exons (363) discovered in any single gene.

The recent discovery of heterozygous human mutations that truncate full-length titin promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the large number of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease.

In order to distinguish between TTN mutations linked to DCM and benign mutations in this gene, investigators at Imperial College London (United Kingdom) coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues.

They found diversity of TTN isoform expression in the heart, defined the relative inclusion of TTN exons in different isoforms, and demonstrated that these data, coupled with the position of the TTNtv, provided a robust strategy to discriminate pathogenic from benign TTNtv. They showed that TTNtv was the most common genetic cause of DCM in ambulant patients in the community, identified clinically important manifestations of TTNtv-positive DCM, and defined the penetrance and outcomes of TTNtv in the general population. The key finding was that TTN mutations in healthy individuals usually occurred in regions of the gene that were not included in the final protein, allowing titin to remain functional.

Senior author Dr. Stuart Cook, professor of clinical and molecular cardiology at Imperial College London, said, "These results give us a detailed understanding of the molecular basis for dilated cardiomyopathy. We can use this information to screen patients' relatives to identify those at risk of developing the disease, and help them to manage their condition early."

The study was published in the January 14, 2014, online edition of the journal Science Translational Medicine.

Related Links:
Imperial College London


Gold Member
Antipsychotic TDM Assays
Saladax Antipsychotic Assays
Verification Panels for Assay Development & QC
Seroconversion Panels
New
Mumps Virus Test
ZEUS ELISA Mumps IgG Test System
New
HIV Test
Anti-HIV (1/2) Rapid Test Kit

Print article

Channels

Clinical Chemistry

view channel
Image: The tiny clay-based materials can be customized for a range of medical applications (Photo courtesy of Angira Roy and Sam O’Keefe)

‘Brilliantly Luminous’ Nanoscale Chemical Tool to Improve Disease Detection

Thousands of commercially available glowing molecules known as fluorophores are commonly used in medical imaging, disease detection, biomarker tagging, and chemical analysis. They are also integral in... Read more

Immunology

view channel
Image: The cancer stem cell test can accurately choose more effective treatments (Photo courtesy of University of Cincinnati)

Stem Cell Test Predicts Treatment Outcome for Patients with Platinum-Resistant Ovarian Cancer

Epithelial ovarian cancer frequently responds to chemotherapy initially, but eventually, the tumor develops resistance to the therapy, leading to regrowth. This resistance is partially due to the activation... Read more

Microbiology

view channel
Image: The lab-in-tube assay could improve TB diagnoses in rural or resource-limited areas (Photo courtesy of Kenny Lass/Tulane University)

Handheld Device Delivers Low-Cost TB Results in Less Than One Hour

Tuberculosis (TB) remains the deadliest infectious disease globally, affecting an estimated 10 million people annually. In 2021, about 4.2 million TB cases went undiagnosed or unreported, mainly due to... Read more

Technology

view channel
Image: The HIV-1 self-testing chip will be capable of selectively detecting HIV in whole blood samples (Photo courtesy of Shutterstock)

Disposable Microchip Technology Could Selectively Detect HIV in Whole Blood Samples

As of the end of 2023, approximately 40 million people globally were living with HIV, and around 630,000 individuals died from AIDS-related illnesses that same year. Despite a substantial decline in deaths... Read more

Industry

view channel
Image: The collaboration aims to leverage Oxford Nanopore\'s sequencing platform and Cepheid\'s GeneXpert system to advance the field of sequencing for infectious diseases (Photo courtesy of Cepheid)

Cepheid and Oxford Nanopore Technologies Partner on Advancing Automated Sequencing-Based Solutions

Cepheid (Sunnyvale, CA, USA), a leading molecular diagnostics company, and Oxford Nanopore Technologies (Oxford, UK), the company behind a new generation of sequencing-based molecular analysis technologies,... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.