Missense variants generally are associated with less severe disease than truncating variants that produce no protein due to nonsense-mediated decay. However, this correlation is not perfect, and sometimes the same variant can be seen both in XLT and in WAS (sometimes within two different members of the same family), a concept in genetics referred to as variable expressivity. Although autoimmune disease and malignancy may occur in both conditions,  patients with loss of WASp are at higher risk. A defect in the CD43 molecule has also been found in WAS patients. CD43, a transmembrane sialoglycoprotein also known as a leukosialin, is part of a greater complex involved in T-cell activation and acts as a sensitive indicator of abnormal, malignant B cell populations. Defects in this molecule may be detrimental to WAS patients, who are at a much higher risk of autoimmune diseases that may be exasperated in later-detected B-cell lymphomas. Diagnosis
The diagnosis can be made on the basis of clinical findings, the peripheral blood smear, and low immunoglobulin levels. Typically, IgM levels are low, IgA levels are elevated, and IgE levels may be elevated; paraproteins are occasionally observed. Skin immunologic testing (allergy testing) may reveal hyposensitivity. Individuals with Wiskott–Aldrich syndrome however are at higher risk for severe food allergies. Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on the basis of low platelets and infections, and bone marrow biopsy may be performed. Decreased levels of WASp are typically observed.
In 2006, a German research group analyzed family members of Wiskotts three cases, and surmised they probably shared a novel frameshift mutation of the first exon of the WASp gene. References
Further reading
GeneReviews/NIH/NCBI/UW entry on WAS-Related Disorders including Wiskott-Aldrich syndrome WAS X-linked thrombocytopenia XLT and X-linked congenital neutropenia XLN
Immune Deficiency Foundation - "Wiskott-Aldrich Syndrome"
Wiskott-Aldrich Foundation


== External links ==