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Bioengineering approach to cardiac regeneration/repair

ABSTRACT: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation are very poorly understood. Here we set out to investigate genotype-phenotype relationships in two siblings with an extensive family history of hypertrophic cardiomyopathy (HCM), both carrying a pathogenic truncating variant in the MYBPC3 gene (p.Lys600Asnfs*2), but who exhibited highly divergent clinical manifestations. The pathogenic MYBPC3 variant was found to be necessary, but not sufficient, to induce iPSC-CM hyperexcitability, suggesting the presence of additional genetic modifiers. Whole-exome sequencing (WES) of the mutant carriers identified a variant of unknown significance (VUS) in the MYH7 gene (p.Ile1927Phe) uniquely present in the individual with severe HCM, the pathogenicity of which was assessed by functionally evaluating iPSC-CMs after editing the variant.

INSTRUMENT(S): -

ORGANISM(S): Homo Sapiens

SUBMITTER: Bellvitge Biomedical Research Institute (IDIBELL)

PROVIDER: PRJEB61786 | EVA | 2023-12-31

REPOSITORIES: EVA

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			Action	DRS
	WES_bio_CR_merged.vcf.csi	Other
	WES_bio_CR_merged.vcf.gz	Vcf
	WES_bio_CR_merged.vcf.gz.csi	Vcf

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