Ambruso et al. (2000) reported a male infant of nonconsanguineous parents who presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. The infant presented at 5 weeks of age with a perirectal abscess and ... Ambruso et al. (2000) reported a male infant of nonconsanguineous parents who presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. The infant presented at 5 weeks of age with a perirectal abscess and failure of the umbilical stump to involute. In the subsequent 4 months, he exhibited recurrent perirectal abscesses, an infected urachal cyst, failure of surgical wounds to heal, and absence of pus in infected areas. Transfusions of neutrophils collected from healthy blood donors were required for the resolution of the abscesses and complete healing of the surgical wounds. The patient showed leukocytosis and neutrophilia, normal levels of serum immunoglobulins, normal complement activity (CH50 and C3), and low-normal numbers of total T and B cells, as well as T-cell subsets for his age. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion production, but had normal expression and upregulation of CD11b (120980). RAC2 constitutes more than 96% of the RAC in neutrophils and is a member of the Rho family of GTPases that regulates the actin cytoskeleton and superoxide anion production. By Western blot analysis of lysates from the patient's neutrophils, Ambruso et al. (2000) found decreased levels of RAC2 protein. Addition of recombinant RAC2 extracts of the patient's neutrophils reconstituted its superoxide anion production in an in vitro assay system.
In an infant with recurrent infections, Ambruso et al. (2000) identified a missense mutation in the RAC2 gene (602049.0001) involving an amino acid that is invariant in all defined GTP-binding proteins.