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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MYH7BHumanhypertrophic cardiomyopathy  ISORGD:1307994 RGD 
MYH7BHumanhypertrophic cardiomyopathy  IAGP DNA:polymorphism:CDS:multiple (human)RGD 
Myh7bRathypertrophic cardiomyopathy  ISORGD:1317507DNA:polymorphism:CDS:multiple (human)RGD 
Myh7bRathypertrophic cardiomyopathy  IMP  RGD 
Myh7bMousehypertrophic cardiomyopathy  ISORGD:1307994 RGD 
Myh7bMousehypertrophic cardiomyopathy  ISORGD:1317507DNA:polymorphism:CDS:multiple (human)RGD 
Myh7bem1BlarRathypertrophic cardiomyopathy  IMP  RGD 
SD-Myh7bem1Blar+/-Rathypertrophic cardiomyopathy  IMP  RGD 
SD-Myh7bem1Blar-/-Rathypertrophic cardiomyopathy  IMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Myh7bRatabnormal myocardial fiber calcium currents  IMP  RGD 
Myh7bem1BlarRatabnormal myocardial fiber calcium currents  IMP  RGD 
SD-Myh7bem1Blar+/-Ratabnormal myocardial fiber calcium currents  IMP  RGD 
SD-Myh7bem1Blar-/-Ratabnormal myocardial fiber calcium currents  IMP  RGD 
Myh7bRatabnormal sarcomere morphology  IMP  RGD 
Myh7bem1BlarRatabnormal sarcomere morphology  IMP  RGD 
SD-Myh7bem1Blar+/-Ratabnormal sarcomere morphology  IMP  RGD 
SD-Myh7bem1Blar-/-Ratabnormal sarcomere morphology  IMP  RGD 
Myh7bRatcardiac fibrosis  IMP  RGD 
Myh7bem1BlarRatcardiac fibrosis  IMP  RGD 
SD-Myh7bem1Blar+/-Ratcardiac fibrosis  IMP  RGD 
SD-Myh7bem1Blar-/-Ratcardiac fibrosis  IMP  RGD 
Myh7bRatdecreased body weight  IMP  RGD 
Myh7bem1BlarRatdecreased body weight  IMP  RGD 
SD-Myh7bem1Blar-/-Ratdecreased body weight  IMP  RGD 
Myh7bRatheart left ventricle hypertrophy  IMP  RGD 
Myh7bem1BlarRatheart left ventricle hypertrophy  IMP  RGD 
SD-Myh7bem1Blar+/-Ratheart left ventricle hypertrophy  IMP  RGD 
SD-Myh7bem1Blar-/-Ratheart left ventricle hypertrophy  IMP  RGD 
Myh7bRatincreased cardiac muscle calcium level  IMP  RGD 
Myh7bem1BlarRatincreased cardiac muscle calcium level  IMP  RGD 
SD-Myh7bem1Blar+/-Ratincreased cardiac muscle calcium level  IMP  RGD 
SD-Myh7bem1Blar-/-Ratincreased cardiac muscle calcium level  IMP  RGD 
Myh7bRatincreased heart left ventricle posterior wall thickness  IMP  RGD 
Myh7bem1BlarRatincreased heart left ventricle posterior wall thickness  IMP  RGD 
SD-Myh7bem1Blar+/-Ratincreased heart left ventricle posterior wall thickness  IMP  RGD 
SD-Myh7bem1Blar-/-Ratincreased heart left ventricle posterior wall thickness  IMP  RGD 
Myh7bRatincreased myocardial fiber size  IMP  RGD 
Myh7bem1BlarRatincreased myocardial fiber size  IMP  RGD 
SD-Myh7bem1Blar+/-Ratincreased myocardial fiber size  IMP  RGD 
SD-Myh7bem1Blar-/-Ratincreased myocardial fiber size  IMP  RGD 
Myh7bRatthick interventricular septum  IMP  RGD 
Myh7bem1BlarRatthick interventricular septum  IMP  RGD 
SD-Myh7bem1Blar+/-Ratthick interventricular septum  IMP  RGD 
SD-Myh7bem1Blar-/-Ratthick interventricular septum  IMP  RGD 

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