Heavy chains familial hypertrophic cardiomyopathy

Geisterfer-Lowrance, A.A., Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W., Seidman, C.E., Seidman, J.G. (1990). A molecular basis for familial hypertrophic cardiomyopathy a p-cardiac myosin heavy chain gene missense mutation. Cell 62, 999-1006,... 

Mutations in the Cardiac (i-Myosin Heavy Chain Gene Are One Cause of Familial Hypertrophic Cardiomyopathy... 

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

In addition, iPSC-CMs have been used to model structural heart diseases, including familial dilated cardiomyopathy (DCM) (Sun et al., 2012) and hypertrophic cardiomyopathy (HCM) (Lan et al., 2013) caused by mutations in cardiac troponin T (cTnT) and myosin heavy chain 7 (MYH7), respectively. In both studies, iPSC-CMs recapitulated the disease phenotype at the cellular level with pharmacological rescue by chronic treatment with p-adrenergic blocker (propranolol or metoprolol) or the L-type Ca channel blocker (verapamil) (Sun et al., 2012 Lan et al., 2013) (Table 22.1). Collectively, these studies reinforce the ability of iPSC-CMs to model channelopathies and cardiomyopathies as well as to test the clinical efficacy of drugs. 

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