A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells

Veronica Astro, Elisabetta Fiacco, Kelly Johanna Cardona-Londoño, Ilario De Toma, Hams Saeed Alzahrani, Jumana Alama, Amal Kokandi, Taha Abo Almagd Abdel-Meguid Hamoda, Majed Felemban, Antonio Adamo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: The transcriptional landscape of Klinefelter syndrome (KS)during early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males induced pluripotent stem cells (iPSCs)obtained from patients with different genomic backgrounds and ethnicities. Design and method: We derived and characterized 15 iPSC lines from four Saudi 47,XXY KS patients and one Saudi 46,XY male. We performed a comparative transcriptional analysis using the Saudi KS-iPSCs and a cohort of European and North American KS-iPSCs. Results: We identified a panel of X-linked and autosomal genes commonly dysregulated in Saudi and European/North American KS-iPSCs vs 46,XY controls. Our findings demonstrate that seven PAR1 and nine non-PAR escape genes are consistently dysregulated and mostly display comparable transcriptional levels in both groups. Finally, we focused on genes commonly dysregulated in both iPSC cohorts and identified several gene-ontology categories highly relevant to KS physiopathology, including aberrant cardiac muscle contractility, skeletal muscle defects, abnormal synaptic transmission, and behavioral alterations. Conclusions: Our results indicate that a transcriptomic signature of X chromosome overdosage in KS is potentially attributable to a subset of X-linked genes sensitive to sex chromosome dosage and escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic makeup.

Original languageEnglish (US)
Article numbere220515
JournalEndocrine Connections
Issue number5
StatePublished - May 2023


  • escape genes
  • induced pluripotent stem cells
  • Klinefelter syndrome
  • pseudoautosomal region
  • X chromosome

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


Dive into the research topics of 'A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells'. Together they form a unique fingerprint.

Cite this