Wiskott-Aldrich syndrome: report of an autosomal dominant variant
B Rocca, A Bellacosa, R De Cristofaro, G Neri, M Della Ventura, N Maggiano, C Rumi and R Landolfi
Department of Medicine, Catholic University School of Medicine, Rome,
Italy.
The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder
originally described as a clinical triad of thrombocytopenia with small
platelets, eczema, and immunodeficiency. Impaired CD43 glycoprotein
expression on lymphocytes is a typical hallmark of this disorder. The CD43
gene is located on chromosome 16, and the WAS gene, WASP, was recently
isolated from the chromosome X p11.22-p11.23. This gene, mutated in WAS
patients, encodes a protein that is likely to play a role in controlling
the expression of CD43. However, the molecular mechanism(s) causing WAS are
not yet known. Herein, we describe a three- generation family in which
clinical and laboratory WAS features were expressed in six of nine subjects
available for study. At variance with classic X-linked WAS, this disorder
was characterized by the presence of thrombocytopenia with a broad spectrum
of platelet size, including giant platelets, and was inherited as an
autosomal dominant trait. This last finding led us to hypothesize a
mutation of the CD43 gene. However, Southern blot analysis failed to detect
structural abnormalities of this gene, and genotype analysis ruled out the
possibility that a CD43 allele might be shared by the affected individuals.
These findings indicate that an alteration(s) of an autosomal gene distinct
from the CD43 gene is responsible for the disease. Thus, results from this
family, providing the first observation of an autosomally transmitted WAS
variant, indicate that genetic mechanism(s) leading to WAS are more complex
than previously recognized.
Volume 87,
Issue 11,
pp. 4538-4543,
06/01/1996
Copyright © 1996 by The American Society of Hematology
