Generation of induced pluripotent stem cells from a patient with hearing loss carrying OPA1 c.1468T>C (p.Cys490Arg) variant

Yen-Hui Chan; Chang-Han Ho; Cheng-Yu Tsai; Ying-Chang Lu; Pei-Hsuan Lin; Ta-Ching Chen; You-Tzung Chen; Cheng-Yen Huang; Tien-Chen Liu; Chuan-Jen Hsu; Chen-Chi Wu

doi:10.1016/j.scr.2022.102903

Generation of induced pluripotent stem cells from a patient with hearing loss carrying OPA1 c.1468T>C (p.Cys490Arg) variant

Stem Cell Res. 2022 Oct:64:102903. doi: 10.1016/j.scr.2022.102903. Epub 2022 Aug 26.

Authors

Affiliations

¹ Department of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
² Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan.
⁴ Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan.
⁶ Gene Knockout/in Cell Line Modeling Core, Human Disease Modeling Center, First Core Laboratory, Branch Office of Research and Development, College of Medicine, National Taiwan University, Taiwan.
⁷ Department of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan. Electronic address: cjhsu@ntu.edu.tw.
⁸ Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: chenchiwu@ntuh.gov.tw.

PMID: 36075118
DOI: 10.1016/j.scr.2022.102903

Abstract

Pathogenic variants of OPA1 have been associated with autosomal dominant optic atrophy (DOA), leading to optic, auditory, and other sensorineural neuropathies and myopathies. Using the Sendai virus delivery system, we generated induced pluripotent stem cells from the peripheral blood mononuclear cells of a female patient with the OPA1 pathogenic variant c.1468T>C (p.Cys490Arg). The resulting induced pluripotent stem cells exhibited a normal karyotype and pluripotency, as confirmed using immunofluorescence staining, and differentiated into three germ layers in vivo. This cellular model is a useful platform for investigating the pathogenic mechanisms of both blindness and deafness related to OPA1 variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
GTP Phosphohydrolases / genetics
Hearing Loss* / genetics
Humans
Induced Pluripotent Stem Cells* / pathology
Leukocytes, Mononuclear / pathology
Mutation
Optic Atrophy, Autosomal Dominant* / genetics
Optic Atrophy, Autosomal Dominant* / pathology

Substances

OPA1 protein, human
GTP Phosphohydrolases