Generation of two induced pluripotent stem cell lines from a patient with Stargardt disease caused by compound heterozygous mutations in the ABCA4 gene

Di Huang; Dan Zhang; Shang-Chih Chen; May Thandar Aung-Htut; Tina M Lamey; Jennifer A Thompson; Terri L McLaren; John N De Roach; Sue Fletcher; Steve D Wilton; Fred K Chen; Samuel McLenachan

doi:10.1016/j.scr.2021.102448

Generation of two induced pluripotent stem cell lines from a patient with Stargardt disease caused by compound heterozygous mutations in the ABCA4 gene

Stem Cell Res. 2021 Jul:54:102448. doi: 10.1016/j.scr.2021.102448. Epub 2021 Jun 24.

Authors

Affiliations

¹ Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Western Australia, Australia.
² Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia.
³ Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Australia.
⁴ Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Nedlands, Western Australia, Australia; Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁵ Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁶ Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Western Australia, Australia.
⁷ Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Nedlands, Western Australia, Australia; Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia; Department of Ophthalmology, Perth Children's Hospital, Nedlands, Western Australia, Australia.
⁸ Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Nedlands, Western Australia, Australia. Electronic address: smclenachan@lei.org.au.

PMID: 34198153
DOI: 10.1016/j.scr.2021.102448

Abstract

Stargardt disease (STGD1) is the most common inherited retinal dystrophy and ABCA4 c.546--10 T>C is the most commonly reported splice mutation. Here, we generated and characterized two induced pluripotent stem cell (iPSC) lines from a STGD1 patient with compound heterozygous mutations in ABCA4 (c.[5461-10 T > C;5603A > T];[4163 T > C;455G > A]). Episomal vectors containing OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed to conduct the reprogramming of patient-derived fibroblasts. Both lines had a normal karyotype, displayed iPSC morphology, expressed pluripotency markers and showed trilineage differentiation potential. These lines can provide a powerful platform for further investigating the pathophysiological consequences of mutations in ABCA4.

Publication types

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

MeSH terms

ATP-Binding Cassette Transporters / genetics
Cell Differentiation
Cell Line
Humans
Induced Pluripotent Stem Cells*
Kruppel-Like Factor 4
Mutation
Stargardt Disease

Substances

ABCA4 protein, human
ATP-Binding Cassette Transporters
KLF4 protein, human
Kruppel-Like Factor 4