Truncated gene may lead to idiopathic dilated cardiomyopathy
Kelvin Lin 42619390
|Table 1: Showing known possible causes for |
Dilated cardiomyopathy (DCM) is a major cause of heart failures, found to be responsible for more than 10,000 deaths annually in United States (Idiopathic dilated cardiomyopathy: A common but mystifying cause of heart failure). The disease is characterized by the dilation and impaired contraction of the left or both ventricles (Jefferies & Towbin 2010). The muscle of the ventricle chamber weakens, causing for the ventricle to become enlarged and weakened, and becomes less efficient at pumping blood. Although there are many known causes for the disease, in more than half of the cases, the cause is unknown (Felker et al. 1999). These cases are classified as idiopathic dilated cardiomyopathy. Without a known cause, prevention and early detection of the disease is unlikely. A recent study by Dr Daniel Herman and his colleagues have identified a gene mutation that explains 25%, a quarter of the idiopathic cases (Herman et al. 2012).
Dr Herman and colleagues have shown that the presence of mutated TTN gene found to be significantly higher in the subjects with idiopathic cases of dilated cardiomyopathy than the control cohort. Their study analysed the DNA of 312 subjects with idiopathic dilated cardiomyopathy, and 249 subjects as controls. 54 of the subjects with DCM were found to have the mutated TTN gene, while 1 subject had mutated TTN gene from the control cohort (Herman et al. 2012). This provides strong evidence that the mutations are associated with DCM.
Family members of 16 subjects with DCM were found to have mutated TTN gene and dilated cardiomyopathy together (Herman et al. 2012), providing strong evidence for coinheritance.
Figure 1: A comparison in the cross-section between a normal heart
and a heart affected by DCM (American Heart Association n.d.)
TTN gene codes for a specific protein, ‘titin’, which is an essential component of the muscle structure, providing flexibility, structure, and stability to the cardiac muscle (Genetics Home Reference 2012). Herman and colleagues posited this gene mutation to cause a truncation in the amino acid sequence of the titin (Herman et al. 2012). As the amino sequence is defective, the protein synthesized is shortened and functions abnormally, leading to defects in the cardiac muscle. Herman et al. suggests this to be the underlying cause for some subjects with idiopathic DCM (Herman et al. 2012).
The treatment of DCM today is focused on limiting the progression of cardiomyopathy process and preventing sudden heart failures (Khoo et al. 2010). However, early detection of DCM is difficult as the diseased subject usually remain asymptomatic until the disease has progressed into a stage where ventricular defect is present (Khoo et al. 2010), and the prognosis is generally poor once the disease is symptomatic (Kaplan & Porter 2011). If TTN gene analysis is included into clinical genetic screenings, earlier diagnosis of DCM and intervention to prevent disease progression may be possible (Khoo et al. 2010).
With further researches on the TTN gene and the implementation new genetic screenings for TTN gene mutation, better treatments may become available and the development of DCM may be prevented in those with DCM caused by the gene.
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