Recurrent fever of unknown origin and unexplained bacteremia in a patient with a novel 4.5 Mb microdeletion in Xp11.23-p11.22.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
received:
24
01
2024
accepted:
19
06
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
1
8
2024
Statut:
epublish
Résumé
Fever of unknown origin (FUO) remains a formidable diagnostic challenge in the field of medicine. Numerous studies suggest an association between FUO and genetic factors, including chromosomal abnormalities. Here, we report a female patient with a 4.5 Mb Xp microdeletion, who presented with recurrent FUO, bacteremia, colitis, and hematochezia. To elucidate the underlying pathogenic mechanism, we employed a comprehensive approach involving single cell RNA sequencing, T cell receptor sequencing, and flow cytometry to evaluate CD4 T cells. Analysis of peripheral blood mononuclear cells revealed augmented Th1, Th2, and Th17 cell populations, and elevated levels of proinflammatory cytokines in serum. Notably, the patient exhibited impaired Treg cell function, possibly related to deletion of genes encoding FOPX3 and WAS. Single cell analysis revealed specific expansion of cytotoxic CD4 T lymphocytes, characterized by upregulation of various signature genes associated with cytotoxicity. Moreover, interferon-stimulated genes were upregulated in the CD4 T effector memory cluster. Further genetic analysis confirmed maternal inheritance of the Xp microdeletion. The patient and her mother exhibited X chromosome-skewed inactivation, a potential protective mechanism against extensive X chromosome deletions; however, the mother exhibited complete skewing and the patient exhibited incomplete skewing (85:15), which may have contributed to emergence of immunological symptoms. In summary, this case report describes an exceptional instance of FUO stemming from an incompletely inactivated X chromosome microdeletion, thereby increasing our understanding of the genetics underpinning FUO.
Identifiants
pubmed: 39090138
doi: 10.1038/s41598-024-65341-5
pii: 10.1038/s41598-024-65341-5
doi:
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
17801Subventions
Organisme : the Kun-hee Lee Seoul National University Hospital Child Cancer & Rare Disease Project, Republic of Korea
ID : 22B-001-0500
Organisme : the National Research Foundation of Korea
ID : NRF-2022M3A9I2017587
Informations de copyright
© 2024. The Author(s).
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