Generation of two hiPSCs lines of two patients carrying truncating mutations in the dimerization domain of filamin C

N M Daya; K Döring; H Zhuge; L Volke; V Stab; J Dietz; M Athamneh; A Roos; H Zaehres; A K Güttsches; L Mavrommatis; M Vorgerd

doi:10.1016/j.scr.2024.103320

Generation of two hiPSCs lines of two patients carrying truncating mutations in the dimerization domain of filamin C

Stem Cell Res. 2024 Apr:76:103320. doi: 10.1016/j.scr.2024.103320. Epub 2024 Jan 27.

Authors

N M Daya¹, K Döring², H Zhuge¹, L Volke¹, V Stab³, J Dietz¹, M Athamneh⁴, A Roos¹, H Zaehres⁵, A K Güttsches¹, L Mavrommatis¹, M Vorgerd⁶

Affiliations

¹ Department of Neurology, Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany.
² Department of Human Genetics, Ruhr-University Bochum, 44801 Bochum, Germany.
³ Department of Endocrinology, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany.
⁴ Department of Clinical Science, Faculty of Medicine, Yarmouk University, Irbid, Jordan.
⁵ Department of Anatomy and Molecular Embryology, Institute of Anatomy, Ruhr-University Bochum, 44801 Bochum, Germany.
⁶ Department of Neurology, Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany. Electronic address: [email protected].

PMID: 38309149
DOI: 10.1016/j.scr.2024.103320

Abstract

Here we introduce the human induced pluripotent stem cell lines (hiPSCs), HIMRi004-A and HIMRi005-A from dermal fibroblasts of a 48-year-old female (HIMRi004-A) carrying missense mutation that translate to the first described filamin C isoform p.W2710X and from a 56-year-old female (HIMRi005-A) carrying a recently described mutation in the same domain p.Y2704X. Both lines are generated via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. The lines display a typical embryonic stem cell-like morphology, express pluripotency markers, retain a normal karyotype (46, XX) and have the differentiation capacity in all three germ layers. The two lines can be used to elucidate the pathomechanisms of FLNC myofibrillar myopathies and to develop novel therapeutic options.

MeSH terms

Cell Differentiation / genetics
Cell Line
Dimerization
Female
Fibroblasts / metabolism
Filamins / genetics
Filamins / metabolism
Humans
Induced Pluripotent Stem Cells* / metabolism
Kruppel-Like Factor 4
Middle Aged
Mutation / genetics

Substances

Filamins
Kruppel-Like Factor 4