Authors: 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
- King Abdullah University of Science and Technology Biological and Environmental Science and Engineering Division, Thuwal, Saudi Arabia
- Sequentia Biotech, Barcelona, Spain.
- Department of Genetic Medicine, King Abdulaziz University Faculty of Medicine, Jeddah, Saudi Arabia.
- King Abdulaziz University Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia.
- Department of Dermatology, King Abdulaziz University Faculty of Medicine, Jeddah, Saudi Arabia.
- Department of Urology, King Abdulaziz University Faculty of Medicine, Jeddah, Saudi Arabia.
- Department of Medical Laboratory Sciences, King Abdulaziz University Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia.
Publication: National Library of Medicine – National Center for Biotechnology Information
Date: March, 2023
The transcriptional landscape of Klinefelter syndrome during early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males iPSCs obtained from patients with different genomic background and ethnicity. 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. We identified a panel of X-linked and autosomal genes commonly dysregulated in Saudi and European/North American KS-iPSCs versus 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 shortened QT interval and aberrant cardiac muscle contractility, skeletal muscle defects, abnormal synaptic transmission, and behavioral alterations.