An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells.

ABSTRACT: Jacobs (JS) and Klinefelter (KS) syndromes, carrying 47,XYY and 47,XXY chromosomes, respectively, are the most prevalent sex-chromosome aneuploidies in males. JS and KS patients share several clinical features, including sterility, hormonal deficits, neurocognitive delay, and skeletal-muscle defects, although the penetrance of these traits in the two syndromes varies. Despite the high incidence, the molecular mechanisms underlying the clinical manifestations in sex aneuploid male patients are still elusive. In this study, we characterize the inaugural cohort of 47,XYY human induced pluripotent stem cells (iPSCs). We perform a comprehensive transcriptional analysis, including 47,XYY and 46,XY primary fibroblasts, iPSCs, and neural stem cells (NSCs), alongside a comparative analysis of 47,XY

SUBMITTER: Astro V 

PROVIDER: S-EPMC12212075 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature