AIMS: Familial hypertrophic cardiomyopathy (HCM) is one the most common heart 
disorders, with gene mutations in the cardiac sarcomere. Studying HCM with 
patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes 
(CMs) would benefit the understanding of HCM mechanism, as well as the 
development of personalized therapeutic strategies.
METHODS AND RESULTS: To investigate the molecular mechanism underlying the 
abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single 
missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched 
from HCM and healthy iPSCs, followed with whole transcriptome sequencing and 
pathway enrichment analysis. A widespread increase of genes responsible for 
'Cell Proliferation' was observed in HCM iPSC-CMs when compared with control 
iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and 
electrophysiological irregularities. Furthermore, disease phenotypes of HCM 
iPSC-CMs were attenuated with pharmaceutical treatments.
CONCLUSION: Overall, this study explored the possible patient-specific and 
mutation-specific disease mechanism of HCM, and demonstrates the potential of 
using HCM iPSC-CMs for future development of therapeutic strategies. 
Additionally, the whole methodology established in this study could be utilized 
to study mechanisms of other human-inherited heart diseases.