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rdf:type |
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lifeskim:mentions |
umls-concept:C0011155,
umls-concept:C0017262,
umls-concept:C0027950,
umls-concept:C0185117,
umls-concept:C0205217,
umls-concept:C0678226,
umls-concept:C1332823,
umls-concept:C1428419,
umls-concept:C1853118,
umls-concept:C1860319,
umls-concept:C2911684
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pubmed:issue |
15
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pubmed:dateCreated |
2010-10-15
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:ChouJanice YJY,
pubmed-author:De RavinSuk SeeSS,
pubmed-author:DingChengchengC,
pubmed-author:DunsmoreKimberly PKP,
pubmed-author:HilligossDianneD,
pubmed-author:JunHyun SikHS,
pubmed-author:KuhnsDouglas BDB,
pubmed-author:MalechHarry LHL,
pubmed-author:MarquesenMarthaM,
pubmed-author:McDermottDavid HDH,
pubmed-author:MurphyPhilip MPM,
pubmed-author:NoelPierreP,
pubmed-author:OjodeTeresaT,
pubmed-author:PaulScott MSM,
pubmed-author:PrielDebra A LongDA,
pubmed-author:SeckGG,
pubmed-author:TakemotoClifford MCM
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2793-802
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pubmed:dateRevised |
2011-10-14
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pubmed:meshHeading |
pubmed-meshheading:20616219-Adolescent,
pubmed-meshheading:20616219-Animals,
pubmed-meshheading:20616219-Child,
pubmed-meshheading:20616219-Female,
pubmed-meshheading:20616219-Gene Expression,
pubmed-meshheading:20616219-Glucose-6-Phosphatase,
pubmed-meshheading:20616219-Glycogen Storage Disease Type I,
pubmed-meshheading:20616219-Homozygote,
pubmed-meshheading:20616219-Humans,
pubmed-meshheading:20616219-Male,
pubmed-meshheading:20616219-Mice,
pubmed-meshheading:20616219-Mice, Inbred C57BL,
pubmed-meshheading:20616219-Mice, Knockout,
pubmed-meshheading:20616219-Mutation, Missense,
pubmed-meshheading:20616219-Neutropenia,
pubmed-meshheading:20616219-Neutrophils,
pubmed-meshheading:20616219-Receptors, CXCR4,
pubmed-meshheading:20616219-Syndrome
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pubmed:year |
2010
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pubmed:articleTitle |
Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis.
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pubmed:affiliation |
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. dmcdermott@niaid.nih.gov
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, N.I.H., Intramural
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