Affiliations: Molecular Immunology Unit, UCL Institute of Child
Health, London, UK | Department of Immunology, Great Ormond Street Hospital
NHS Trust, Great Ormond Street, London, UK
Note: [] Corresponding author: Adrian J. Thrasher, UCL Institute of Child
Health, Molecular Immunology Unit, 30 Guilford Street, London, WC1N 1EH, UK.
Tel.: +44 (0)20 7905 2289; Fax: +44 (0)20 7905 2810; E-mail:
a.thrasher@ich.ucl.ac.uk
Abstract: Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive primary
immunodeficiency characterised by immune dysregulation, microthrombocytopaenia,
eczema and lymphoid malignancies. Mutations in the WAS gene can lead to
distinct syndrome variations which largely, although not exclusively, depend
upon the mutation. Premature termination and deletions abrogate Wiskott-Aldrich
syndrome protein (WASp) expression and lead to severe disease (WAS). Missense
mutations usually result in reduced protein expression and the phenotypically
milder X-linked thrombocytopenia (XLT) or attenuated WAS [1-3]. More
recently however novel activating mutations have been described that give rise
to X-linked neutropenia (XLN), a third syndrome defined by neutropenia with
variable myelodysplasia [4-6]. WASP is key in transducing signals from
the cell surface to the actin cytoskeleton, and a lack of WASp results in
cytoskeletal defects that compromise multiple aspects of normal cellular
activity including proliferation, phagocytosis, immune synapse formation,
adhesion and directed migration.
