Study investigators encountered a female Becker muscular dystrophy (BMD) carrier with advanced heart failure (HF) and identified a stop-gain variant in procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 () as a potential second-hit variant. Isogenic induced pluripotent stem cells (iPSCs) with dominant expression of WT-, Δ45-48-, or Δ45-48- with corrected variant were established. Microforce testing using 3-dimensional self-organized tissue rings (SOTRs) generated from iPSC-derived cardiomyocytes (iPSC-CMs) demonstrated that correction of the heterozygous variant did not improve the reduced force, but it significantly recovered the reduced stiffness in Δ45-48- SOTRs. Correction of the variant restored collagen synthesis in iPSC-CMs. Our findings revealed the pathogenesis underlying advanced HF in a female BMD carrier.
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| http://dx.doi.org/10.1016/j.jacbts.2022.11.007 | DOI Listing |
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