WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype

@article{Imai2003WASPS,
  title={WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype},
  author={Kohsuke Imai and Shigeaki Nonoyama and Hans D. Ochs},
  journal={Current Opinion in Allergy and Clinical Immunology},
  year={2003},
  volume={3},
  pages={427-436}
}
Purpose of reviewWiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT), characterized by chronic microthrombocytopenia with and without immunodeficiency, are caused by mutations of the WAS protein (WASP) gene. WASP has been reported to interact with many cytoplasmic molecules linking cellular signaling to the actin cytoskeleton. In this review we will focus on recent molecular findings that provide a better understanding of the pathogenesis of this complex disease and explore the… 
Analysis of the domain specific function of the Wiskott Aldrich Syndrome Protein, in vitro and in vivo
TLDR
It is demonstrated that mutant WASp which causes WAS in patients has normal molecular activity, but the regulation of mutant Wasp degradation is impaired in myeloid cells.
Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome.
TLDR
A full understanding of the mechanisms leading to defects in T, B, and dendritic cells still remains poorly understood is still needed to further implement new therapeutic strategies for this peculiar immunodeficiency.
A Complex of Wiskott-Aldrich Syndrome Protein with Mammalian Verprolins Plays an Important Role in Monocyte Chemotaxis1
  • S. Tsuboi
  • Biology, Medicine
    The Journal of Immunology
  • 2006
TLDR
The results suggest that WASP and mammalian verprolins function as a unit in monocyte chemotaxis and that the activity of this unit is critical to establish cell polarization.
Platelets in Wiskott‐Aldrich syndrome: Victims or executioners?
TLDR
An overview of the state‐of‐the art platelets as immune modulators at the interface between hemostasis and the immune system, which suggests that these cells may have a direct role in the pathogenesis of immune dysregulation in WAS.
Whole Exome Sequencing of an X-linked Thrombocytopenia Patient with Normal Sized Platelets
TLDR
A novel de novo mutation in WAS gene which truncates WASp to half of its normal size was determined as the only cause of clinical manifestation.
A Disease Mechanism Underlying Bleeding in Wiskott-Aldrich Syndrome
TLDR
It is demonstrated that blocking WASP binding to CIB reduces binding of talin to the β3 cytoplasmic tail, resulting in impaired activation of αIIbβ3.
Characterization of Wiskott-Aldrich syndrome (WAS) mutants using Saccharomyces cerevisiae.
TLDR
Using the las17Delta strain, missense mutations in the gene encoding WASP are analyzed and it is found that 13 mutations cause the classic WAS in humans without affecting the WASP-WIP complex formation, but may affect the activity of the complex.
Recent advances in the biology of WASP and WIP
TLDR
This review has summarized recent developments in the biology of WASP and the role of WIP in regulating WASP function and also discusses WASP-independent functions of Wip.
Mechanisms of WASp-mediated hematologic and immunologic disease.
TLDR
This review highlights recent advances that have enhanced the understanding of the mechanisms by which molecular defects cause hematologic and immunologic disease in Wiskott-Aldrich syndrome.
...
...

References

SHOWING 1-10 OF 98 REFERENCES
Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein.
TLDR
Impaired WASP-WIP interaction may contribute to Wiskott-Aldrich syndrome, and point mutant analyses in the two-hybrid system and in vitro show impairment of WasP-wIP interaction with three WASP missense mutants known to cause WAS.
Novel mutations in the Wiskott‐Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes
TLDR
It is concluded that mutation analysis at the DNA level is not sufficient for predicting clinical course and studies at the transcript and protein level are needed for a better assessment.
Involvement of wiskott-aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway.
TLDR
An in vivo reconstitution system demonstrated that WASP is physically associated with Btk and can serve as the substrate for Btk, and identification of the phosphorylation site of WASP in reconstituted cells allowed us to evaluate the catalytic specificity of Btk.
Wiskott-Aldrich syndrome in a female.
TLDR
A 14-month-old girl with a history of WAS in her family who presented with thrombocytopenia, small platelets, and immunologic dysfunction has a defect in the mechanisms that lead in disease-free WAS carriers to preferential survival/proliferation of cells bearing the active wild-type X chromosome.
The pleckstrin homology domain of the Wiskott-Aldrich syndrome protein is involved in the organization of actin cytoskeleton.
TLDR
Overexpression of WASP with a missense mutation in the N-terminus of the PH domain failed to induce the large cluster formation in COS-7 cells even in the presence of FCS, and it is suggested that the binding of PIP(2) to thePH domain is necessary for WASP to function properly.
Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype.
TLDR
It is concluded that missense mutations affecting the PH domain (exons 1 to 3) of WASP inhibit less important functions of the protein and result in a mild phenotype, and that complex mutations affect the 3' portion of WasP interfere with crucial functions ofThe protein and cause classic WAS.
The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene.
TLDR
Findings provide direct evidence that XLT and WAS are caused by mutations of the same gene and suggest that severe clinical phenotypes are associated with complex mutations.
...
...