A mutation in the largest human gene causes 25 percent of a type of inherited heart disease, according to scientists in the USA. The information could be incorporated into current genetic tests to provide early diagnosis and clinical intervention.
The condition, known as familial dilated cardiomyopathy (DCM), causes the heart to become enlarged, losing the ability to pump blood efficiently, and can lead to heart failure by middle age.
Study co-leader Dr Jonathan Seidman of Harvard Medical School explained that the gene, called TTN, has been implicated in the disease before, but due to its large size it has been very difficult to sequence and analyse.
The study, published in the New England Journal of Medicine, screened the entire sequence of the TTN gene in 312 people with dilated cardiomyopathy, 231 with another form of heart disease and 249 without heart disease. This identified 72 mutations in the TTN gene, resulting in a shorter version of titin, which lacked regions important for regulating contraction in cardiac muscle cells.
'Early diagnosis of any disease, including DCM, can allow interventions that may prevent some of the devastating outcomes, such as sudden cardiac death from an arrhythmia or development of heart failure', said study co-leader Dr Christine Seidman of Brigham and Women's Hospital. 'By knowing that TTN mutations account for a substantial amount of idiopathic DCM, we now will have the opportunity for early diagnosis in lots of at-risk individuals, and any person who has a family member with idiopathic DCM'.
Dr Jonathan Seidman added that half of the DCM patients had a first degree relative with a TTN mutation and of these 95 percent had some sign of heart disease by age 40.
Dr Gordon Tomaselli, president of the American Heart Association and chief of cardiology at Johns Hopkins Medicine in Baltimore, said that the study is important for both researchers and patients. Currently, genetic tests are available that screen for the other known causes of cardiomyopathy. According to Dr Tomaselli we could expect to see TTN testing being added to current genetic screens within months.