Generation and characterization of human iPSC lines from two patients with therapy-resistant epilepsy carrying nonsense heterozygous variants in the SMC1A gene

  • Stem Cell Res. 2025 Jun 16:87:103752. doi: 10.1016/j.scr.2025.103752.
Marianna Paulis  1 ,  Maddalena Di Nardo  2 ,  Lucia Susani  3 ,  Angela La Grua  4 ,  Antonio Musio  5
Affiliations
  • 1. IRCCS Humanitas Research Hospital, Rozzano 20089, Italy; UOS Milan Unit, Institute for Genetic and Biomedical Research, (IRGB), National Research Council (CNR), Milan 20138, Italy. Electronic address: [email protected].
  • 2. Institute for Biomedical Technologies (ITB), National Research Council (CNR), Pisa 56124, Italy.
  • 3. IRCCS Humanitas Research Hospital, Rozzano 20089, Italy; UOS Milan Unit, Institute for Genetic and Biomedical Research, (IRGB), National Research Council (CNR), Milan 20138, Italy.
  • 4. IRCCS Humanitas Research Hospital, Rozzano 20089, Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan 20129, Italy.
  • 5. Institute for Biomedical Technologies (ITB), National Research Council (CNR), Pisa 56124, Italy. Electronic address: [email protected].
PMID: 40541047 DOI: 10.1016/j.scr.2025.103752
Abstract

Different SMC1A variants contribute to a spectrum of phenotypes. Missense or small in-frame deletions are associated with Cornelia de Lange syndrome (CdLS) while SMC1A truncation variants have been detected in subjects with a clinical phenotype different from CdLS, with moderate-to-severe intellectual disability (ID) and pharmaco-resistant epilepsy. We generated two human iPSC lines from two patients with pharmaco-resistant epilepsy carrying nonsense heterozygous c.901C > T (p.E323*) and c.3103C > T (p.R1035*) variants in the SMC1A gene. These cell lines will be a valuable resource for in vitro disease modeling and drug testing for pharmaco-resistant epilepsy due to SMC1A variants.

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