Public Release: 

'Titin' gene mutations will help identify patients at risk of heart failure

Imperial College London

A new study has identified genetic mutations that cause the heart condition dilated cardiomyopathy (DCM), paving the way for more accurate diagnosis.

By sequencing the gene encoding the muscle protein titin in more than 5,000 people, scientists have worked out which variations are linked to disease, providing information that will help screen high-risk patients.

Titin gene mutations were previously associated with DCM, a leading cause of inherited heart failure, but many people have variations in the genetic code that are completely benign.

The new study, published in Science Translational Medicine, sorts the harmful from the harmless mutations, giving doctors a directory to interpret patients' DNA sequences.

The information could also help researchers develop therapies to prevent or treat heart disease caused by titin mutations.

The study was led by researchers at Imperial College London and Royal Brompton & Harefield NHS Foundation Trust.

Around one in 250 people are estimated to have DCM. It causes the heart muscle to become thin and weak, often leading to heart failure.

Mutations in the titin gene that make the protein shorter, or truncated, are the most common cause of DCM, accounting for about a quarter of cases. But truncations in the gene are common - around one in 50 people have one - and most are not harmful, making it difficult to develop a useful genetic test.

The researchers sequenced the titin gene from 5,267 people, including healthy volunteers and patients with DCM, and analysed the levels of titin in samples of heart tissue. The results showed that mutations that cause DCM occur at the far end of the gene sequence. Mutations in healthy individuals tend to occur in parts of the gene that aren't included in the final protein, allowing titin to remain functional.

Professor Stuart Cook, from the Medical Research Council (MRC) Clinical Sciences Centre at Imperial College London, who led the study, 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 research was funded by the MRC, the British Heart Foundation, Fondation Leducq, the Wellcome Trust, the National Institute for Health Research (NIHR) Royal Brompton Cardiovascular Biomedical Research Unit and the NIHR Imperial Biomedical Research Centre.

Professor Dudley Pennell, director of the NIHR Royal Brompton Cardiovascular Biomedical Research Unit, said: "This research reveals which genetic mutations are bad and which are there purely as bystanders. It will benefit patients with cardiomyopathy and enable us to reassure relatives who do not have the disease, allowing them to be discharged from clinic and preventing needless anxiety and unnecessary expensive tests."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Determining which mutations in titin are harmful and which are not has been difficult, in part because titin is one of the largest human proteins.

"This study defines, for the first time, a comprehensive list of mutations in the titin gene, which of these are associated with dilated cardiomyopathy, and which are harmless. This information will be extremely valuable for correct future diagnosis and treatment as we enter an era when many people's genes will be sequenced."


For more information please contact:

Sam Wong
Research Media Officer
Imperial College London
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. A.M. Roberts et al. 'Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.' Sci. Transl. Med. 7, 270ra6 (2015).

2. Related Press Telephone Conference: An embargoed press teleconference is planned for 11:00 a.m. U.S. ET, Tuesday, 13 January 2015.

All information released during the press teleconference will remain under embargo until 2:00 p.m. U.S. ET (7pm GMT), Wednesday, 14 January 2015. The speakers will be Dr James Ware from the Royal Brompton & Harefield NHS Foundation Trust & Imperial College London, UK, and from Harvard Medical School in Boston, MA; Dr Angharad Roberts from Imperial College London, UK; Dr Christine Seidman at Brigham and Women's Hospital, Harvard Medical School, and Howard Hughes Medical Institute in Boston, MA; and Dr Stuart Cook from Duke-NUS Graduate Medical School in Singapore, and NHLI, Imperial College in London, UK.

Dialing instructions for reporters are as follows: In the United States/Canada, call toll-free: +1-800-374-0748; outside the United States/Canada, call toll number: +1-706-634-9041. Reporters interested in joining the telecon are asked to send an email to to pre-register and obtain the passcode. A real-time transcript will be viewable at To log in, please email for the confirmation number. The embargoed press teleconference, for journalists only, is being organized by the journal Science Translational Medicine and its publisher, AAAS, the nonprofit international science society. Audio files and a transcript will be available shortly after the call.

3. About Imperial College London

Imperial College London is one of the world's leading universities. The College's 14,000 students and 7,500 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.

Founded in 1907, Imperial builds on a distinguished past - having pioneered penicillin, holography and fibre optics - to shape the future. Imperial researchers work across disciplines to improve global health, tackle climate change, develop sustainable energy technology and address security challenges. This blend of academic excellence and its real-world application feeds into Imperial's exceptional learning environment, where students participate in research to push the limits of their degrees.

Imperial nurtures a dynamic enterprise culture, where collaborations with industrial, healthcare and international partners are the norm. In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Imperial has nine London campuses, including Imperial West: a new 25 acre research and innovation centre in White City, west London. At Imperial West, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale.

4. About the National Institute for Health Research

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (

5. About Royal Brompton & Harefield NHS Foundation Trust

Royal Brompton & Harefield NHS Foundation Trust is a national and international specialist heart and lung centre based in Chelsea, London and Harefield, Middlesex. The Trust helps patients from all age groups who have heart and lung conditions and is the country's largest centre for the treatment of adult congenital heart disease.

In March 2008, the Trust was one of 16 Biomedical Research Units (BRUs) established by the National Institute for Health Research (NIHR) to undertake translational clinical research. It awarded a four-year grant worth over £10m to a partnership of the Trust and Imperial College London, to fund both respiratory and cardiac BRUs at the Trust. A further five-year grant of almost £20m was awarded by the NIHR in August 2011.This funding enables pioneering research into some of the most complex heart and lung conditions affecting patients in the UK and around the world.

In December 2013, Secretary of State for Health, Jeremy Hunt, officially opened a brand new genetics and genomics laboratory at Royal Brompton Hospital, The £2 million facility - a joint venture between the Trust and Imperial College London - is a flagship development of the NIHR Royal Brompton BRU, translating research into NHS practice. The state-of-the-art laboratory provides patients with vastly improved access to genetic tests and enables much quicker gene testing for those clinically diagnosed with - or a family member who is at risk of - an inherited cardiac condition.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.