Document Detail


Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis.
MedLine Citation:
PMID:  20616219     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations in more than 15 genes are now known to cause severe congenital neutropenia (SCN); however, the pathologic mechanisms of most genetic defects are not fully defined. Deficiency of G6PC3, a glucose-6-phosphatase, causes a rare multisystem syndrome with SCN first described in 2009. We identified a family with 2 children with homozygous G6PC3 G260R mutations, a loss of enzymatic function, and typical syndrome features with the exception that their bone marrow biopsy pathology revealed abundant neutrophils consistent with myelokathexis. This pathologic finding is a hallmark of another type of SCN, WHIM syndrome, which is caused by gain-of-function mutations in CXCR4, a chemokine receptor and known neutrophil bone marrow retention factor. We found markedly increased CXCR4 expression on neutrophils from both our G6PC3-deficient patients and G6pc3(-/-) mice. In both patients, granulocyte colony-stimulating factor treatment normalized CXCR4 expression and neutrophil counts. In G6pc3(-/-) mice, the specific CXCR4 antagonist AMD3100 rapidly reversed neutropenia. Thus, myelokathexis associated with abnormally high neutrophil CXCR4 expression may contribute to neutropenia in G6PC3 deficiency and responds well to granulocyte colony-stimulating factor.
Authors:
David H McDermott; Suk See De Ravin; Hyun Sik Jun; Qian Liu; Debra A Long Priel; Pierre Noel; Clifford M Takemoto; Teresa Ojode; Scott M Paul; Kimberly P Dunsmore; Dianne Hilligoss; Martha Marquesen; Jean Ulrick; Douglas B Kuhns; Janice Y Chou; Harry L Malech; Philip M Murphy
Related Documents :
12241879 - Association between activating mutations of calcium-sensing receptor and bartter's synd...
24269399 - Silent sinus syndrome. clinical case.
11704759 - Mutations in ptpn11, encoding the protein tyrosine phosphatase shp-2, cause noonan synd...
19577669 - A 56-year-old female patient with facio-oculo-acoustico-renal syndrome (foar) syndrome....
23949889 - Intellectual disability, unusual facial morphology and hand anomalies in sibs.
412969 - Variant of iduronidase deficient mucopolysaccharidoses: further evidence for genetic he...
19588649 - Gitelman's syndrome.
19482959 - Caring for the student with wolff-parkinson-white syndrome.
7751169 - Ciguatera: current concepts.
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Intramural     Date:  2010-07-08
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-15     Completed Date:  2010-11-05     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2793-802     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. dmcdermott@niaid.nih.gov
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Animals
Child
Female
Gene Expression
Glucose-6-Phosphatase / genetics*
Glycogen Storage Disease Type I / genetics*
Homozygote
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation, Missense
Neutropenia / congenital*,  enzymology,  genetics*
Neutrophils / metabolism
Receptors, CXCR4 / genetics*
Syndrome
Chemical
Reg. No./Substance:
0/CXCR4 protein, human; 0/CXCR4 protein, mouse; 0/Receptors, CXCR4; EC 3.1.3.9/Glucose-6-Phosphatase; EC 3.1.3.9./G6PC3 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value.
Next Document:  Recipient T lymphocytes modulate the severity of antibody-mediated transfusion-related acute lung in...