Crossman Vanessa G, Tiong Chrystal F, Coles Chantal A, Bozaoglu Kiymet, Forbes Robin, Yiu Eppie M, Ruparelia Avnika A, Currie Peter D, Vlahos Katerina, Howden Sara E, North Kathryn N, Lamandé Shireen R, Houweling Peter J
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Pediatrics, The University of Melbourne, Victoria, Australia.
Stem Cell Res. 2025 Apr;84:103673. doi: 10.1016/j.scr.2025.103673. Epub 2025 Feb 5.
To produce an in vitro model of Bethlem myopathy, we reprogrammed the peripheral blood mononuclear cells (PBMCs) of a patient with a heterozygous COL6A1 c.1056 + 2T > A mutation at the exon/intron 14 boundary of the COL6A1 gene to induced pluripotent stem cells (iPSCs). Using CRISPR/Cas9 gene editing, we corrected the mutation to generate an isogenic control line. Both the patient and isogenic control iPSCs show a normal karyotype, express pluripotency markers and can differentiate into cell states that represent the three embryonic germ layers (endoderm, mesoderm and ectoderm). These cell lines will be differentiated and used to explore disease mechanisms and evaluate novel therapeutics for Bethlem myopathy.
