{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:29Z","timestamp":1784557049583,"version":"3.55.0"},"reference-count":39,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,27]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The transcriptional landscape of Klinefelter syndromeduring 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and method<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-22-0515","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T10:59:54Z","timestamp":1679914794000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":7,"title":["A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells"],"prefix":"10.1530","volume":"12","author":[{"given":"Veronica","family":"Astro","sequence":"first","affiliation":[{"name":"Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Fiacco","sequence":"additional","affiliation":[{"name":"Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Johanna","family":"Cardona-Londo\u00f1o","sequence":"additional","affiliation":[{"name":"Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilario","family":"De Toma","sequence":"additional","affiliation":[{"name":"Sequentia Biotech SL, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hams Saeed","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumana","family":"Alama","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Kokandi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha Abo-Almagd Abdel-Meguid","family":"Hamoda","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed","family":"Felemban","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-3547","authenticated-orcid":true,"given":"Antonio","family":"Adamo","sequence":"additional","affiliation":[{"name":"Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Lancet","first-page":"273","article-title":"Klinefelter\u2019s syndrome","volume":"364","author":"Lanfranco","year":"2004","unstructured":"Lanfranco FKamischke AZitzmann M & Nieschlag E. 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