A Novel Intronic Mutation Reduces HAX1 Level and is Associated With Severe Congenital Neutropenia.
Journal
Journal of pediatric hematology/oncology
ISSN: 1536-3678
Titre abrégé: J Pediatr Hematol Oncol
Pays: United States
ID NLM: 9505928
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
received:
04
09
2020
accepted:
14
12
2020
pubmed:
10
2
2021
medline:
17
2
2022
entrez:
9
2
2021
Statut:
ppublish
Résumé
Severe congenital neutropenia (SCN) is a rare disease. Autosomal recessive forms of SCN are more frequent in countries where consanguineous marriages are common. In this report, we describe a 54-day-old female with neutropenia who presented with ecthyma gangrenosum. Clinical exome sequencing was used to identify the mutation. HAX1 messenger RNA and isoforms were examined by real-time quantitative and conventional polymerase chain reaction. Bone marrow aspiration was stained by hematoxylin and eosin. Granulocytes were tested for apoptosis upon H2O2 exposure. T-cell proliferation was tested by flow cytometry. Clinical exome sequencing revealed a novel homozygous acceptor splice site mutation in intron 3 of HAX1 (c.505-1G>C), which reduced both isoforms A and B of HAX1 messenger RNA. The Western blot studies showed a complete absence of HAX1 protein. The purified neutrophils from the patient showed increased apoptosis upon H2O2 exposure, whereas T-cell proliferative responses to various stimuli were intact. The patient was treated with combined antibiotics, filgrastim, and placed on antibiotics prophylaxis. To the best of our knowledge, our data provide the first experimental evidence for HAX1 deficiency because of a splice site mutation. Although 3 other splice site variants have been deposited in databases, functional studies were missing. This novel variant of HAX1 may explain the SCN and secondary infections in our patients.
Identifiants
pubmed: 33560082
doi: 10.1097/MPH.0000000000002071
pii: 00043426-202201000-00016
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
HAX1 protein, human
0
RNA Splice Sites
0
Hydrogen Peroxide
BBX060AN9V
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e62-e67Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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