Generation of two iPSC lines from patients with inherited central core disease and concurrent malignant hyperthermia caused by dominant missense variants in the RYR1 gene

Joshua S Clayton; Christina Vo; Jordan Crane; Carolin K Scriba; Safaa Saker; Thierry Larmonier; Edoardo Malfatti; Norma B Romero; Gianina Ravenscroft; Nigel G Laing; Rhonda L Taylor

doi:10.1016/j.scr.2024.103410

Generation of two iPSC lines from patients with inherited central core disease and concurrent malignant hyperthermia caused by dominant missense variants in the RYR1 gene

Stem Cell Res. 2024 Mar 30:77:103410. doi: 10.1016/j.scr.2024.103410. Online ahead of print.

Authors

Affiliations

¹ Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia; Centre for Medical Research, University of Western Australia, QEII Medical Centre, Nedlands, WA, Australia. Electronic address: joshua.clayton@perkins.org.au.
² Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia; Centre for Medical Research, University of Western Australia, QEII Medical Centre, Nedlands, WA, Australia.
³ Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia; Centre for Medical Research, University of Western Australia, QEII Medical Centre, Nedlands, WA, Australia; Neurogenetics Laboratory, Department of Diagnostic Genomics, PP Block, QEII Medical Centre, Nedlands, WA, Australia.
⁴ Genethon, DNA and Cell Bank, 91000 Evry, France.
⁵ APHP, Centre de Référence de Pathologie Neuromusculaire Nord-Est-Ile-de-France, Henri Mondor Hospital, France; Université Paris Est, U955, INSERM, IMRB, F-94010 Créteil, France.
⁶ Sorbonne Université, Myology Institute, Neuromuscular Morphology Unit, Center for Research in Myology, GH Pitié-Salpêtrière, Paris, France; Centre de Référence de Pathologie Neuromusculaire Paris-Est, GHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.

PMID: 38583293
DOI: 10.1016/j.scr.2024.103410

Abstract

RYR1 variants are the most common genetic cause of congenital myopathies, and typically cause central core disease (CCD) and/or malignant hyperthermia (MH). Here, we generated iPSC lines from two patients with CCD and MH caused by dominant RYR1 variants within the central region of the protein (p.Val2168Met and p.Arg2508Cys). Both lines displayed typical iPSC morphology, uniform expression of pluripotency markers, trilineage differentiation potential, and had normal karyotypes. These are the first RYR1 iPSC lines from patients with both CCD and MH. As these are common CCD/MH variants, these lines should be useful to study these conditions and test therapeutics.