RGD Reference Report - MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway. - Rat Genome Database

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

Authors: Chen, Peng  Li, Zongzhe  Nie, Jiali  Wang, Hong  Yu, Bo  Wen, Zheng  Sun, Yang  Shi, Xiaolu  Jin, Li  Wang, Dao-Wen 
Citation: Chen P, etal., Sci China Life Sci. 2020 Sep;63(9):1347-1362. doi: 10.1007/s11427-019-1627-y. Epub 2020 Mar 17.
RGD ID: 126925946
Pubmed: PMID:32207065   (View Abstract at PubMed)
DOI: DOI:10.1007/s11427-019-1627-y   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertrophic cardiomyopathy  ISOMyh7b (Rattus norvegicus)126925946; 126925946 RGD 
hypertrophic cardiomyopathy  IAGP 126925946DNA:polymorphism:CDS:multiple (human)RGD 
hypertrophic cardiomyopathy  ISOMYH7B (Homo sapiens)126925946; 126925946DNA:polymorphism:CDS:multiple (human)RGD 
hypertrophic cardiomyopathy  IMP 126925946; 126925946; 126925946; 126925946 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Myh7b  (myosin heavy chain 7B)
Myh7bem1Blar  (myosin heavy chain 7B; CRISPR/Cas9 induced mutant 1, Blar)

Genes (Mus musculus)
Myh7b  (myosin, heavy chain 7B, cardiac muscle, beta)

Genes (Homo sapiens)
MYH7B  (myosin heavy chain 7B)

Additional Information