Purpose of review
Wiskott-Aldrich syndrome is caused by mutations of the Wiskott-Aldrich syndrome protein
gene, which codes for a cytoplasmic protein with multiple functions. This review will focus on recent progress in understanding the molecular basis of Wiskott-Aldrich syndrome and its ramifications for the cure of this lethal disease.
The discovery of the causative gene has revealed a spectrum of clinical phenotypes demonstrating a strong genotype/phenotype correlation. The discovery of unique functional domains of Wiskott-Aldrich syndrome protein
has been instrumental in defining mechanisms that control activation of Wiskott-Aldrich syndrome protein
. Long-term follow up of patients undergoing hematopoietic stem cell transplantation
has led to important modifications of the procedure. Studies of Wiskott-Aldrich syndrome protein
-deficient cell lines and wasp-knockout mice have paved the way for possible gene therapy
Summary Wiskott-Aldrich syndrome protein
gene mutations result in four clinical phenotypes: classic Wiskott-Aldrich syndrome and X-linked thrombocytopenia, intermittent thrombocytopenia and neutropenia. Wiskott-Aldrich syndrome protein
is a signaling molecule and instrumental for cognate and innate immunity, cell motility and protection against autoimmune disease. The success of hematopoietic stem cell transplantation
is related to the recipient's age, donor selection, the conditioning regimen and the extent of reconstitution. Since Wiskott-Aldrich syndrome protein
is expressed exclusively in hematopoietic stem cells, and because Wiskott-Aldrich syndrome protein
exerts a strong selective pressure, gene therapy
is expected to cure the disease.