ABSTRACT
Variants in MYH7 cause cardiomyopathies as well as myosin storage myopathy and Laing early-onset distal myopathy (MPD1). MPD1 is characterized by muscle weakness and atrophy usually beginning in the lower legs. Here, we generated iPSC lines from lymphoblastoid cells of three unrelated individuals heterozygous for the most common MPD1-causing variant; p.Lys1617del. iPSC lines showed typical morphology, expressed pluripotency markers, demonstrated trilineage differentiation potential, and had a normal karyotype. These lines represent the first iPSCs derived from MPD1 patients and complement existing MPD1 animal models. They can provide in vitro platforms to better understand and model MPD1 pathomechanisms and test therapies.
Subject(s)
Cardiac Myosins , Distal Myopathies , Induced Pluripotent Stem Cells , Myosin Heavy Chains , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/pathology , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , Distal Myopathies/genetics , Distal Myopathies/pathology , Distal Myopathies/metabolism , Cardiac Myosins/genetics , Cardiac Myosins/metabolism , Male , Female , Cell Line , Cell Differentiation , AdultABSTRACT
RYR1 variants are a common cause of congenital myopathies, including multi-minicore disease (MmD) and central core disease (CCD). Here, we generated iPSC lines from two CCD patients with dominant RYR1 missense variants that affect the transmembrane (pore) and SPRY3 protein domains (p.His4813Tyr and p.Asn1346Lys, respectively). Both lines had typical iPSC morphology, expressed canonical pluripotency markers, exhibited trilineage differentiation potential, and had normal karyotypes. Together with existing RYR1 iPSC lines, these represent important tools to study and develop treatments for RYR1-related myopathies.
Subject(s)
Induced Pluripotent Stem Cells , Mutation, Missense , Ryanodine Receptor Calcium Release Channel , Humans , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/metabolism , Induced Pluripotent Stem Cells/metabolism , Myopathy, Central Core/genetics , Myopathy, Central Core/pathology , Myopathy, Central Core/metabolism , Adult , Cell Line , Male , Cell Differentiation , FemaleABSTRACT
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.
