Heart failure & cardiomyopathies
Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice
Authors' conclusion
Novel loss-of-function PRDM16 variant impairs myocardial development resulting in noncompaction cardiomyopathy in humans and mice associated with altered TGF-β signaling.
Study context
- Population
- Individuals with PRDM16 loss-of-function variants and pediatric LV noncompaction cardiomyopathy
- Participants
- 2 probands
Methodological detailsiPSC-derived cardiomyocytes, CRISPR knock-in mouse model, H9c2 cardiomyoblasts
- iPSC-derived cardiomyocytes
- CRISPR knock-in mouse model
- H9c2 cardiomyoblasts
Main finding
As reported in the abstract
- PRDM16-Q187X proband (LV noncompaction cardiomyopathy) had infant-onset HF
- Proband iPSC-cardiomyocytes: significantly impaired myocyte proliferation and increased apoptosis, with transcriptional dysregulation of cardiac maturation genes incl. TGF-β-associated transcripts
- Homozygous Prdm16Q187X/Q187X mice: underdeveloped compact myocardium, embryonically lethal
- Heterozygous Prdm16Q187X/WT mice: significantly smaller ventricular dimensions, heightened fibrosis, age-dependent loss of TGF-β expression
- In H9c2 cardiomyoblasts, PRDM16 binds TGFB3 promoter and represses its transcription
Original publication
Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice. Circ Heart Fail. Published 19 December 2023. doi:10.
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