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MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway.

08:00 EDT 17th March 2020 | BioPortfolio

Summary of "MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway."

Hypertrophic cardiomyopathy (HCM) is a common genetic disease, predominantly caused by mutations in cardiac sarcomere genes; however, whether MYH7B causes HCM is not known. In this study, 549 unrelated patients with HCM and 500 healthy-controls were screened using targeted sequencing and whole exome sequencing together. We observed seven variants in MYH7B causing HCM in 8/549 patients, which accounted for 1.46% of HCM cases. Of these seven variants, three likely pathogenic variants in MYH7B co-segregating with 5 HCM patients were identified in three HCM pedigrees without other HCM-associated variants. Myh7b knockout rats were generated and cardiac functions were detected by Millar pressure-volume catheterization and echocardiography. Spontaneous HCM phenotypes, cellular disarray and cardiac fibrosis were observed in both Myh7b/Myh7b rats. Transcriptome sequencing showed that calcium is the key mediator of cardiac hypertrophy in Myh7b knockout. Subsequent analysis confirmed over-activation of CaMK-signaling pathway in cardiomyocytes of Myh7b rats. Furthermore, MYH7B expression in human and rat hearts was identified and microRNA-208a and microRNA-499 levels are unchanged in HCM patients and Myh7b/Myh7b rats. This study is the first to identifyMYH7B variants as cause of HCM, which account for 1.46% of pathogenesisin HCM patients. Activation of CaMK-signaling pathway may be involved in its pathophysiology.

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Name: Science China. Life sciences
ISSN: 1869-1889
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Medical and Biotech [MESH] Definitions

An autosomal dominant inherited form of HYPERTROPHIC CARDIOMYOPATHY. It results from any of more than 50 mutations involving genes encoding contractile proteins such as VENTRICULAR MYOSINS; cardiac TROPONIN T; ALPHA-TROPOMYOSIN.

A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).

A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).

An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)

Isoforms of MYOSIN TYPE II, specifically found in the ventricular muscle of the HEART. Defects in the genes encoding ventricular myosins result in FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.

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