Genome editing of patient-derived iPSCs identifies a deep intronic variant causing aberrant splicing in hemophilia A.

ABSTRACT: The importance of genetic diagnosis for patients with hemophilia has been recently demonstrated. However, the pathological variant cannot be identified in some patients. Here, we aimed to identify the pathogenic intronic variant causing hemophilia A using induced pluripotent stem cells (iPSCs) from patients and genome editing. We analyzed siblings with moderate hemophilia A and without abnormalities in the F8 exon. Next-generation sequencing of the entire F8 revealed 23 common intron variants. Variant effect predictor software indicated that the deep intronic variant at c.5220-8563A>G (intron 14) might act as a splicing acceptor. We developed iPSCs from patients and used genome editing to insert the elongation factor 1α promoter to express F8 messenger RNA (mRNA). Then, we confirmed the ex

SUBMITTER: Hiramoto T 

PROVIDER: S-EPMC10690555 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature