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. 2025 Oct 10;137(9):1226-1228.
doi: 10.1161/CIRCRESAHA.125.326637. Epub 2025 Sep 15.

Functional Analysis of a Homozygous MYBPC3 Null Allele in Human Pediatric Patients

Jeffrey S Bennett  1 , Patrick T Wood  2 , Katherine L Dominic  2 , Christine S Moravec  3 , Kenneth S Campbell  4 , Julian E Stelzer  2
Affiliations

Functional Analysis of a Homozygous MYBPC3 Null Allele in Human Pediatric Patients

Jeffrey S Bennett et al. Circ Res. .
No abstract available

Keywords: cardiac myosin; heart failure; hypertrophy; mutation; myocardium.

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Conflict of interest statement

None.

Figures

Figure:
Figure:
A. Representative echo (Ai) from a male child diagnosed with systolic heart failure at 5 years old, initially diagnosed with severe dilated cardiomyopathy. Genetic testing identified biallelic MYBPC3 splice variants. Following decompression via LVAD placement, marked hypertrophy of the left ventricle was noted (Aii). He underwent a successful orthotopic heart transplant, representing the oldest documented diagnosis of the biallelic hypertrophic cardiomyopathy B. Representative western blot and total protein stain show the expression of cMyBP-C in myofibrils. C. Myosin heavy chain quantification. Porcine left atrium (LA) + porcine left ventricle (LV) ~50–50% α/β-myosin. The youngest donor tissue sample showed detectable amounts of α-myosin; however, the oldest donor, c.3330+2T>G and HF myocardium did not contain detectable amounts of α-myosin, thus it is likely that myosin isoform switching is irrelevant to this study. D. Representative Pro-Q Diamond and Sypro-Ruby-stained SDS gels show the phosphorylation and expression of myofilament proteins, represented as average/heart. E. Due to procurement limitations of c.3330+2T>G patient tissue, two hearts were used from each group, with 5 myocardial fibers from each group used in the measurements. N=2 hearts, K=5 myocardial fibers per group. Myocardial fibers were incubated in 0.5U PKA (P2645, Sigma) for 1hr as described previously . Mechanical experiments were analyzed with a two-way linear mixed-effects model using SAS software (version 9.1.3; SAS Institute, Cary, NC). Statistical analysis was performed to provide a quantitative comparison between groups, however due to the sample size, p-values should be interpreted within the limited scope of the data set. Results are reported as mean ± SD.
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References

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