Generation of human-induced pluripotent stem cells from a patient with Beckwith-Wiedemann syndrome

Hum Cell. 2025 Jun 27;38(4):121. doi: 10.1007/s13577-025-01247-2.

Abstract

Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder mainly caused by an imprinting abnormality in the chromosome 11p15.5 region. It is rare and sporadic with unclear etiology and pathogenesis. We identified a family with a clustering of BWS cases arising from methylation abnormality of IC1 region. An induced pluripotent stem-cell line (BWS iPSC) was generated from peripheral blood mononuclear cells (PBMCs) of one affected family member using a non-integrating reprogramming method. This cell line could be further differentiated into multiple lineages, enabling us to determine the relationship of the expression of abnormal imprinting genes in BWS to cellular phenotypes, thus elucidating the pathogenic mechanisms of BWS. In future, the multi-lineage cells can be used to test various innovative therapies, providing conceptual validation for the treatment of BWS.

Keywords: Beckwith–Wiedemann syndrome; Epigenetic modification; Imprinting disturbance; Rare disease; iPSC.

MeSH terms

  • Beckwith-Wiedemann Syndrome* / genetics
  • Beckwith-Wiedemann Syndrome* / pathology
  • Cell Differentiation / genetics
  • Cell Line
  • Cells, Cultured
  • Cellular Reprogramming
  • Chromosomes, Human, Pair 11 / genetics
  • DNA Methylation / genetics
  • Female
  • Genomic Imprinting / genetics
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Leukocytes, Mononuclear / cytology
  • Male