Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype

• الحاوية / القاعدة: Scientific Reports
• المؤلفون الرئيسيون: Magdalena Koczkowska, Marcin Jąkalski, Dorota Birkholz-Walerzak, Anna Kostecka, Mariola Iliszko, Magdalena Wójcik, Krzysztof Lewandowski, Katarzyna Milska-Musa, Patrick G. Buckley, Kinga Drężek, Ulana Juhas, Ewa Kuziemska, Agnieszka Maciejewska, Ryszard Pawłowski, Bartosz Wasąg, Natalia Filipowicz, Katarzyna Chojnowska, Urszula Ławrynowicz, Jan P. Dumanski, Beata S. Lipska-Ziętkiewicz, Jakub Mieczkowski, Arkadiusz Piotrowski
• التنسيق: مقال
• اللغة: الإنجليزية
• منشور في: Nature Portfolio 2022-12-01
• الوصول للمادة أونلاين: https://doi.org/10.1038/s41598-022-25308-w

Abstract Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband’s long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis. Although comprehensive cytogenetic analysis showed seemingly near perfect balance between 45, X and 48, XYYY cell populations, scRNA-seq revealed widespread differences in genotype distribution among immune cell fractions, specifically in monocytes, B- and T-cells. These results were confirmed at DNA level by digital-droplet PCR on flow-sorted immune cell types. Furthermore, deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45, X B-lymphocytes and other known genes associated with hematological malignancies. Together with the standard hematological results, showing increased fractions of monocytes and CD4+/CD8+T lymphocytes ratio, long-term personalized hemato-oncological surveillance was recommended in the reported patient.