Transcriptome Sequencing of Patients With Hypertrophic Cardiomyopathy Reveals Novel Splice-Altering Variants in MYBPC3.

ABSTRACT:

Background

Transcriptome sequencing can improve genetic diagnosis of Mendelian diseases but requires access to tissue expressing disease-relevant transcripts. We explored genetic testing of hypertrophic cardiomyopathy using transcriptome sequencing of patient-specific human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). We also explored whether antisense oligonucleotides (AOs) could inhibit aberrant mRNA splicing in hiPSC-CMs.

Methods

We derived hiPSC-CMs from patients with hypertrophic cardiomyopathy due to MYBPC3 splice-gain variants, or an unresolved genetic cause. We used transcriptome sequencing of hiPSC-CM RNA to identify pathogenic splicing and used AOs to inhibit this splicing.

Results

Transcriptome sequencing of hiPSC-CMs confirmed a

SUBMITTER: Holliday M 

PROVIDER: S-EPMC8284365 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature