Generation of induced pluripotent stem cell lines from three LGMD R1 patients carrying CAPN3 hypomorphic intronic variant c.1746-20C > G

Stem Cell Res. 2025 Sep:87:103803. doi: 10.1016/j.scr.2025.103803. Epub 2025 Aug 13.

Abstract

Calpainopathy is a progressive autosomal recessive limb girdle muscular dystrophy (LGMD R1) caused by variants in the calpain 3 (CAPN3) gene. We have shown that the hypomorphic intronic mutation c.1746-20C > G, which is common in Latvia (MAF 0.237), causes incorrect splicing of the CAPN3 products that in combination with c.643 T > C variant in trans position leads to the development of LGMD clinical symptoms. Our project aims to generate calpainopathy patient-derived induced pluripotent stem cells (iPSCs) and create a disease model that recapitulates unique CAPN3 variant.

MeSH terms

  • Calpain* / genetics
  • Calpain* / metabolism
  • Cell Line
  • Female
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Induced Pluripotent Stem Cells* / pathology
  • Introns* / genetics
  • Male
  • Muscle Proteins* / genetics
  • Muscle Proteins* / metabolism
  • Muscular Dystrophies, Limb-Girdle* / genetics
  • Muscular Dystrophies, Limb-Girdle* / metabolism
  • Muscular Dystrophies, Limb-Girdle* / pathology
  • Mutation

Substances

  • Calpain
  • CAPN3 protein, human
  • Muscle Proteins