Dataset related to article "Impaired CXCR4 internalization but normal calcium mobilization in patients with mild WHIM syndrome"

This record contains raw data related to article  "Impaired CXCR4 internalization but normal calcium mobilization in patients with mild WHIM syndrome"

WHIM syndrome is an inherited error of immunity caused by autosomal dominant heterozygous mutation in CXCR4. The disorder is characterized by neutropenia/leukopenia due to retention of mature neutrophils in bone marrow, recurrent bacterial infections, treatment-refractory warts, and hypogammaglobulinemia. All CXCR4 mutations, with CXCR4^R334X being the most frequent, cause the truncation of the last 10 to 19 amino acids of the carboxy-terminal domain of the receptor; this defect prevents CXCR4 internalization, enhances calcium mobilization and ERK phosphorylation, and results in increased chemotaxis in response to the unique ligand CXCL12. Herein, we describe three siblings presenting neutropenia and myelokathexis, but normal lymphocyte count and immunoglobulin levels, carrying the novel CXCR4^Leu317fsX3 mutation that leads to complete truncation of the intracellular tail. The analysis of CXCR4 functions in cells with the CXCR4^L317fsX3 mutation reveals unique signaling features as compared to the CXCR4^R334X mutation. CXCR4^L317fsX3 mutation impairs CXCR4 downregulation and β-arrestins recruitment in response to CXCL12, without affecting other signaling events including ERK1/2 phosphorylation, calcium mobilization and chemotaxis, all processes typically enhanced in cells carrying the CXCR4^R334X mutation. Our findings suggest that the CXCR4^L317fsX3 mutation may be causative of a mild form of WHIM syndrome, not associated to an augmented CXCR4 response to CXCL12.