Familial Hypertrophic Cardiomyopathy Mutations of the Myosin Regulatory Light Chain Remove Myosin Load Sensitivity

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-Myosin Heavy Chain Gene Mutations in Familial Hypertrophic Cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is a genetic disorder arising from mutations in sarcomeric protein genes. Human genetic studies have implicated at least 9 different genes in FHC, emphasizing the enormous genetic and allelic heterogeneity associated with FHC.1 -Myosin heavy chain ( MyHC, MYH7) is the most commonly mutated gene in FHC, and at least 60 different MYH7 gene mutations have...

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Functional Consequences of Mutations in the Myosin Regulatory Light Chain Associated with Hypertrophic Cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular wall thickening, myofilament disarray and abnormal echocardiography findings. Molecular genetic studies have defined FHC as a disease of the sarcomere caused by mutations in all major sarcomeric proteins, such as ┚-myosin heavy chain (44%), myosin binding protein C (35%), regulatory lig...

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Cardiomyopathy-linked myosin regulatory light chain mutations disrupt myosin strain-dependent biochemistry.

Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in sarcomeric proteins including the myosin regulatory light chain (RLC). Two such FHC mutations, R58Q and N47K, located near the cationic binding site of the RLC, have been identified from population studies. To examine the molecular basis for the observed phenotypes, we exchanged endogenous RLC from native porcine cardiac myosi...

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Mutations of the light meromyosin domain of the beta-myosin heavy chain rod in hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (HCM) is caused by mutations in 9 sarcomeric protein genes. The most commonly affected is beta-myosin heavy chain (MYH7), where missense mutations cluster in the head and neck regions and directly affect motor function. Comparable mutations have not been described in the light meromyosin (LMM) region of the myosin rod, nor would these be expected to directly...

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ژورنال

عنوان ژورنال: Biophysical Journal

سال: 2010

ISSN: 0006-3495

DOI: 10.1016/j.bpj.2009.12.1163