Key result
iPSC-CMs carrying the MYH6-R443P variant contracted more slowly (40 vs 47 contractions/min, P<0.05) and exhibited slower shortening and relaxation rates compared to wild-type cells.
Why the study?
Hypoplastic left heart syndrome is a severe form of congenital heart disease, but its etiology remains largely unknown.
Population
iPSC-derived cardiomyocytes from an HLHS-affected family trio carrying an MYH6-R443P head domain variant
Comparison
MYH6-R443P variant vs corrected or unaffected control iPSC-CMs
Design
In vitro translational and CRISPR/Cas9 gene editing study
Authors
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Hypothesis-generating for MYH6 editing in HLHS; leaves open clinical translation from iPSC-CM models.
Absolute Event Rate: 40% vs 47%
p-value: p=<0.05
The MYH6-R443P variant causes sarcomere disorganization and decreased contractility in iPSC-CMs, which can be rescued by CRISPR/Cas9 gene editing, providing mechanistic insight into HLHS pathogenesis.
Kim et al. (2020) studied Hypoplastic left heart syndrome (HLHS) (n=27). MYH6-R443P variant vs. Wild-type (WT) MYH6 was evaluated on Contraction rate (contractions/min) at differentiation day 20-23 (p=<0.05). iPSC-CMs carrying the MYH6-R443P variant contracted more slowly (40 vs 47 contractions/min, P<0.05) and exhibited slower shortening and relaxation rates compared to wild-type cells.
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