Familial dilated cardiomyopathy with troponin T K210del mutation.

Background: It has been estimated that more than 30% of patients with idiopathic dilated cardiomyopathy have a familial form of the disease. The most frequent pattern of inheritance is autosomal dominant and several genes or loci have been implicated, coding for sarcomeric or cytoskeleton proteins. Most of the genotype-phenotype correlations are still under study, but a particular mutation, K210del in the troponin T gene, has been identified in four different families with severe forms of DCM. The pathogenesis of this mutation has been inferred by functional studies but its transmission has not been demonstrated, perhaps due to the high mortality of the affected family members. The aim of this work was to investigate the prevalence of the K210del mutation in Portuguese and Mozambican families with dilated cardiomyopathy.

Methods: We evaluated 27 probands with familial DCM. Forty idiopathic (sporadic) DCM patients and 100 non-related healthy individuals were used as controls. Mutational analysis was performed by amplification of exon 13 of the troponin T gene by the polymerase chain reaction (PCR), determination of molecular weight of PCR products and further sequencing.

Results: The K210del mutation in the cardiac troponin T gene was identified in one of the DCM families which presented an aggressive form of the disease, with a high incidence of sudden death, and need for heart transplant at young age. One affected member had sustained left ventricular function recovery after diagnosis.

Conclusions: These results reinforce previous work by others, indicating that this mutation is a bad prognostic factor in familial forms of DCM. The K210del mutation in the troponin T gene, like other mutations in the troponin complex, seems to be especially prevalent in families with rapidly progressive DCM or sudden cardiac death at young age.