|
|
Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-02-0388.
Submitted February 5, 2002
Accepted June 3, 2002
Wiskott-Aldrich syndrome in a female
Maxim I Lutskiy, Yoji Sasahara, Dianne M Kenney, Fred S Rosen, and Eileen Remold-O'Donnell*
Center for Blood Research, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
Department of Immunology, Children's Hospital, Boston, MA, USA
* Corresponding author; email: remold{at}cbr.med.harvard.edu.
Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by thrombocytopenia, eczema and various degrees of immune deficiency. Carriers of mutated WASP have non-random X-chromosome inactivation in their blood cells and are disease free. We report a 14-month old female with a history of WAS in her family who presented with thrombocytopenia, small platelets and immunological dysfunction. Sequencing of the WASP gene showed that the patient is heterozygous for the splice site mutation previously found in one of her relatives with WAS. Sequencing of all WASP exons revealed no other mutation. Levels of WASP protein in blood mononuclear cells were 60% of normal. Flow cytometry after intracellular staining of PBMC with WASP MoAb revealed both WASPbright and WASPdim populations. X-chromosome inactivation in the patient's blood cells was found to be random, demonstrating that both maternal and paternal active X-chromosomes are present. These findings indicate that the female patient has a defect in the mechanisms that lead in disease-free WAS carriers to preferential survival/proliferation of cells bearing the active wildtype X-chromosome. Whereas the patient's lymphocytes are skewed towards WASPbright cells, ~ 65% of her monocytes and the majority of her B-cells (CD19+) are WASPdim. Her naive T cells (CD3+CD45RA+) include WASPbright and WASPdim populations; but her memory T cells (CD3+CD45RA-) are all WASPbright. After activation in vitro of T cells, all cells exhibited CD3+CD45RA- phenotype and most were WASPbright with active paternal (wildtype) X-chromosome, suggesting selection against the mutated WASP allele during terminal T-cell maturation/differentiation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. I. Lutskiy, F. S. Rosen, and E. Remold-O'Donnell
Genotype-Proteotype Linkage in the Wiskott-Aldrich Syndrome
J. Immunol.,
July 15, 2005;
175(2):
1329 - 1336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Wada, S. H. Schurman, G. J. Jagadeesh, E. K. Garabedian, D. L. Nelson, and F. Candotti
Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family
Blood,
September 1, 2004;
104(5):
1270 - 1272.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Konno, T. Wada, S. H. Schurman, E. K. Garabedian, M. Kirby, S. M. Anderson, and F. Candotti
Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineages
Blood,
January 15, 2004;
103(2):
676 - 678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Takada, H. Kanegane, A. Nomura, K. Yamamoto, K. Ihara, Y. Takahashi, S. Tsukada, T. Miyawaki, and T. Hara
Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation
Blood,
January 1, 2004;
103(1):
185 - 187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
