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

Posted: January 15, 2015 at 1:41 am

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."

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

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