Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Scientific reports - 12(2022), 1 vom: 02. Dez., Seite 20854 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Koczkowska, Magdalena [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.12.2022 Date Revised 11.01.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-022-25308-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM349733198 |
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| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Jąkalski, Marcin |e verfasserin |4 aut | |
| 700 | 1 | |a Birkholz-Walerzak, Dorota |e verfasserin |4 aut | |
| 700 | 1 | |a Kostecka, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Iliszko, Mariola |e verfasserin |4 aut | |
| 700 | 1 | |a Wójcik, Magdalena |e verfasserin |4 aut | |
| 700 | 1 | |a Lewandowski, Krzysztof |e verfasserin |4 aut | |
| 700 | 1 | |a Milska-Musa, Katarzyna |e verfasserin |4 aut | |
| 700 | 1 | |a Buckley, Patrick G |e verfasserin |4 aut | |
| 700 | 1 | |a Drężek, Kinga |e verfasserin |4 aut | |
| 700 | 1 | |a Juhas, Ulana |e verfasserin |4 aut | |
| 700 | 1 | |a Kuziemska, Ewa |e verfasserin |4 aut | |
| 700 | 1 | |a Maciejewska, Agnieszka |e verfasserin |4 aut | |
| 700 | 1 | |a Pawłowski, Ryszard |e verfasserin |4 aut | |
| 700 | 1 | |a Wasąg, Bartosz |e verfasserin |4 aut | |
| 700 | 1 | |a Filipowicz, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Chojnowska, Katarzyna |e verfasserin |4 aut | |
| 700 | 1 | |a Ławrynowicz, Urszula |e verfasserin |4 aut | |
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| 700 | 1 | |a Lipska-Ziętkiewicz, Beata S |e verfasserin |4 aut | |
| 700 | 1 | |a Mieczkowski, Jakub |e verfasserin |4 aut | |
| 700 | 1 | |a Piotrowski, Arkadiusz |e verfasserin |4 aut | |
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