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Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci U S A 2000 Apr 25;97(9):4654-9 PMID: 10758162 PMCID: PMC18288

Pubmed ID



A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.

Author List

Ambruso DR, Knall C, Abell AN, Panepinto J, Kurkchubasche A, Thurman G, Gonzalez-Aller C, Hiester A, deBoer M, Harbeck RJ, Oyer R, Johnson GL, Roos D


Julie A. Panepinto MD, MSPH Professor in the Pediatrics department at Medical College of Wisconsin


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MESH terms used to index this publication - Major topics in bold

Antigens, CD
Chemotaxis, Leukocyte
Guanosine 5'-O-(3-Thiotriphosphate)
Guanosine Diphosphate
Immunologic Deficiency Syndromes
Macrophage-1 Antigen
NADPH Oxidases
Reference Values
rac GTP-Binding Proteins
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad