SLC26A4 C.317C > A Variant: Functional Analysis and Patient‐Derived Induced Pluripotent Stem Line Development DOI Creative Commons

Yijing Li,

Tao Sun,

Sang Hu

et al.

Molecular Genetics & Genomic Medicine, Journal Year: 2025, Volume and Issue: 13(4)

Published: April 1, 2025

ABSTRACT Background SLC26A4 is the second most common cause of hereditary hearing loss worldwide. This gene predominantly harbors pathogenic variants, including splice, nonsense, and missense. Although missense variants are relatively common, their specific effects on protein function remain unclear. Consequently, there an urgent need to establish in vitro system investigate how these impact function. Methods Genetic testing was conducted determine types underlying genetic patients. Following this, we employed plasmid transfection evaluate both expression levels protein's subcellular localization. Thereafter, transformed peripheral blood mononuclear cells (PBMCs) from proband into induced pluripotent stem (iPSCs) through Sendai virus‐mediated transduction. Results revealed that carried compound heterozygous variants: c.919‐2A > G c.317C A. The A variant markedly decreased mRNA its encoded protein. Additionally, it led accumulation cytoplasm as aggregates. We successfully reprogrammed verified iPSCs retained pluripotency, differentiation potential, integrity. Conclusion These results provide important insights mechanisms by which lead loss.

Language: Английский

SLC26A4 C.317C > A Variant: Functional Analysis and Patient‐Derived Induced Pluripotent Stem Line Development DOI Creative Commons

Yijing Li,

Tao Sun,

Sang Hu

et al.

Molecular Genetics & Genomic Medicine, Journal Year: 2025, Volume and Issue: 13(4)

Published: April 1, 2025

ABSTRACT Background SLC26A4 is the second most common cause of hereditary hearing loss worldwide. This gene predominantly harbors pathogenic variants, including splice, nonsense, and missense. Although missense variants are relatively common, their specific effects on protein function remain unclear. Consequently, there an urgent need to establish in vitro system investigate how these impact function. Methods Genetic testing was conducted determine types underlying genetic patients. Following this, we employed plasmid transfection evaluate both expression levels protein's subcellular localization. Thereafter, transformed peripheral blood mononuclear cells (PBMCs) from proband into induced pluripotent stem (iPSCs) through Sendai virus‐mediated transduction. Results revealed that carried compound heterozygous variants: c.919‐2A > G c.317C A. The A variant markedly decreased mRNA its encoded protein. Additionally, it led accumulation cytoplasm as aggregates. We successfully reprogrammed verified iPSCs retained pluripotency, differentiation potential, integrity. Conclusion These results provide important insights mechanisms by which lead loss.

Language: Английский

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