The open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells.

Mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASP) are responsible for Wiskott-Aldrich syndrome and WASP is a major actin regulator in the cytoplasm. Although rare gain-of-function mutations in the WASP gene are known to result in X-linked neutropenia (XLN), the molecular pathogenesis of XLN is not fully understood. In this study, we showed that all reported constitutively activating mutants (L270P, S272P and I294T) of WASP were hyperphosphorylated by Src family tyrosine kinases and demonstrated higher actin polymerization activities compared with wild-type (WT) WASP.

Characterization of a novel nonsense mutation in the interleukin-7 receptor alpha gene in a Korean patient with severe combined immunodeficiency.

Although it has been suggested that defective interleukin 7 receptor (IL-7R) signaling is one of the principal causes of severe combined immunodeficiency disease (SCID) in mice and humans, little is known about the molecular and clinical characteristics of human IL-7Ralpha mutations. We report a novel mutation of the IL-7Ralpha gene in a Korean SCID patient with a greatly diminished T-cell count but normal numbers of B-cells and natural killer (NK) cells. Using direct sequencing and restriction fragment length polymorphism analysis, we identified a C-->T nucleotide change at position 638.