Human 'knockouts' of CSF3 display severe congenital neutropenia.
GCSF
neutropenia
recurrent infection
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
07
08
2023
received:
12
06
2023
accepted:
08
08
2023
pubmed:
24
8
2023
medline:
24
8
2023
entrez:
23
8
2023
Statut:
ppublish
Résumé
Colony-stimulating factor 3 (CSF3) is a key factor in neutrophil production and function, and recombinant forms have been used clinically for decades to treat congenital and acquired neutropenia. Although biallelic inactivation of its receptor CSF3R is a well-established cause of severe congenital neutropenia (SCN), no corresponding Mendelian disease has been ascribed to date to CSF3. Here, we describe three patients from two families each segregating a different biallelic inactivating variant in CSF3 with SCN. Complete deficiency of CSF3 as a result of nonsense-mediated decay (NMD) could be demonstrated on RT-PCR using skin fibroblasts-derived RNA. The phenotype observed in this cohort mirrors that documented in mouse and zebrafish models of CSF3 deficiency. Our results suggest that CSF3 deficiency in humans causes a novel autosomal recessive form of SCN.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
477-480Informations de copyright
© 2023 British Society for Haematology and John Wiley & Sons Ltd.
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