Metabolic abnormalities in G6PC3-deficient human neutrophils result in severe functional defects
| Autor: | John Murphy, Daniel R. Ambruso, Angelina Baroffio, Alexander D. Tran, Michael Ellison, Julie A. Reisz, Christopher M. McKinney, Natalie J. Briones, Angelo D'Alessandro |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Neutropenia Neutrophils G6PC3 Granulocyte Compound heterozygosity medicine.disease_cause Phagocytes Granulocytes and Myelopoiesis 03 medical and health sciences 0302 clinical medicine Internal medicine Granulocyte Colony-Stimulating Factor medicine Congenital Bone Marrow Failure Syndromes Humans Missense mutation Child Congenital Neutropenia Mutation biology business.industry Hematology medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology Glucose-6-Phosphatase biology.protein business 030217 neurology & neurosurgery Glucose 6-phosphatase |
| Zdroj: | Blood Adv |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2020002225 |
| Popis: | Severe congenital neutropenia type 4 (SCN-4) is an autosomal recessive condition in which mutations in the G6PC3 gene encoding for the catalytic 3 subunit of glucose-6-phosphatase-β result in neutropenia, neutrophil dysfunction, and other syndromic features. We report a child with SCN-4 caused by compound heterozygous mutations in G6PC3, a previously identified missense mutation in exon 6 (c.758G>A[p.R235H]), and a novel missense mutation in exon 2 (c.325G>A[p.G109S]). The patient had recurrent bacterial infections, inflammatory bowel disease, neutropenia, and intermittent thrombocytopenia. Administration of granulocyte colony–stimulating factor (G-CSF) resolved the neutropenia and allowed for detailed evaluation of human neutrophil function. Random and directed migration by the patient’s neutrophils was severely diminished. Associated with this were defects in CD11b expression and F-actin assembly. Bactericidal activity at bacteria/neutrophil ratios >1:1 was also diminished and was associated with attenuated ingestion. Superoxide anion generation was |
| Databáze: | OpenAIRE |
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