Pathogenic variants damage cell compositions and single cell transcription in cardiomyopathies

“Only this level of resolution allows us to see that cardiomyopathies do not uniformly trigger the same pathological pathways. Rather, different mutations evoked specific and some shared responses that lead to heart failure. These genotype-specific responses point to the importance of genotyping.”

“Our findings hold enormous potential for rethinking how we treat heart failure and point to the importance of understanding its root causes and the mutations that lead to changes that may alter how the heart functions. This is fundamental research, but it identifies targets that can be experimentally pursued to propel future therapeutics. Our findings also point to the importance of genotyping — not only does genotyping empower research but it can also lead to better, personalized treatment for patients.”

“We investigated pathogenic gene variants in heart tissue at the single-cell level, which allowed us to map precisely how specific pathogenic variants drive cardiac dysfunction. To our knowledge, this is the first such analysis conducted in cardiac tissue, and we hope this approach can be used to study other types of genetic heart diseases.”