학술논문
Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype.
Document Type
Article
Author
Koczkowska, Magdalena; Jąkalski, Marcin; Birkholz-Walerzak, Dorota; Kostecka, Anna; Iliszko, Mariola; Wójcik, Magdalena; Lewandowski, Krzysztof; Milska-Musa, Katarzyna; Buckley, Patrick G.; Drężek, Kinga; Juhas, Ulana; Kuziemska, Ewa; Maciejewska, Agnieszka; Pawłowski, Ryszard; Wasąg, Bartosz; Filipowicz, Natalia; Chojnowska, Katarzyna; Ławrynowicz, Urszula; Dumanski, Jan P.; Lipska-Ziętkiewicz, Beata S.
Source
Subject
*RNA sequencing
*HEALTH risk assessment
*SEX chromosome abnormalities
*KARYOTYPES
*CELL populations
*DISEASE risk factors
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Language
ISSN
2045-2322
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. [ABSTRACT FROM AUTHOR]