NEW YORK (Reuters Health) - Mutations in the cardiac troponin gene family have been identified in patients with idiopathic dilated cardiomyopathy (DCM), according to a report in the November 16th Journal of the American College of Cardiology.
“Troponin C was identified as a novel disease gene in dilated cardiomyopathy,” Dr. Jens Mogensen from Skejby University Hospital, Aarhus N, Denmark told Reuters Health. “Mutations in the troponin complex appear to be associated with a severe prognosis in dilated cardiomyopathy.”
Dr. Mogensen and colleagues in the UK examined the relationship between genotype and clinical phenotype in families with the troponin C mutation TNNC1 or the troponin T mutation TNNT2.
The authors identified TNNC1 mutations in 8 individuals and TNNT2 mutations in 13 individuals with DCM. Five individuals died of heart failure, six received a cardiac transplant within 6 months of diagnosis, and four experienced sudden unexplained death, a total of 71% overall.
The average of 2.6 deaths per family with troponin disease was significantly higher than that observed in other families with hereditary DCM (0.7 deaths/family), the report indicates.
Functional studies of the mutated troponin C and T proteins showed altered troponin protein-protein interactions, the researchers note, some with impaired and one with enhanced interactions.
Histological examination of myocardial tissue from eight patients showed varying degrees of nonspecific abnormalities, the results indicate, but no features characteristic of hypertrophic cardiomyopathy or storage disease.
“Physicians should be aware that idiopathic dilated cardiomyopathy is a condition that is often hereditary,” Dr. Mogensen said. “It is important to obtain a family history of the patient in relation to other relatives with cardiac disease or incidents of sudden death.”
“Patients who carry these mutations should receive treatment in accordance with generally accepted guidelines for heart failure therapy,” Dr. Mogensen said. “At this stage we do not have evidence to support that healthy gene carriers without signs or symptoms of disease would benefit from prophylactic medical therapy.”
After more healthy mutation carriers are been identified, it will be “essential to conduct a randomized trial to investigate the potential benefits of prophylactic medical therapy,” Dr. Mogensen added. “We are in the process of further characterizing the effect of the mutations on protein-protein interaction in various in-vitro test systems.”
However, editorialists Drs. Jeffrey A. Towbin from Baylor College of Medicine, Houston, and R. John Solaro from University of Chicago, urge caution “regarding genotype-phenotype correlation interpretations.”
“Whether these mutations determine the outcome or whether the small number of patients and potential selection bias is responsible for the appearance of a cause and effect relationship remains to be proven,” they add.
Source: J Am Coll Cardiol 2004;44:2033-2043. [ Google search on this article ]
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