Articles
  

Detection of Six Novel Mutations in WASP Gene in Fifteen Iranian Wiskott-Aldrich Patients

Abstract

Wiskott-Aldrich syndrome (WAS) is a life-threatening X-linked recessive immunodeficiency disease described as a clinical triad of thrombocytopenia,  eczema, and recurrent infections, caused by mutations of the WAS protein (WASP) gene. The milder form of this disease is X-Linked thrombocytopenia  (XLT) that  presents only as platelet abnormalities. Mutation analysis for 15 boys with Wiskott-Aldrich syndrome was performed. Five previously reported mutations and six novel mutations including G8X, R41X, D283E, P412fsX446, E464X, and AfsX358 were detected.

1. Blundell MP, Bouma G, Calle Y, Jones GE, Kinnon C, Thrasher AJ. Improvement of migratory defects in a murine model of Wiskott-Aldrich syndrome gene therapy. Mol Ther 2008; 16(5):836-44.
2. Snapper SB, Meelu P, Nguyen D, Stockton BM, Bozza P,Alt FW, et al. WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo. J Leukoc Biol 2005; 77(6):993-8.
3. Morales-Tirado V, Sojka DK, Katzman SD, Lazarski CA,Finkelman FD, Urban JF, et al. Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function Blood; 2010; 115(17):3498-507.
4. Massaad MJ, Ramesh N, Le Bras S, Giliani S, Notarangelo LD, Al-Herz W, et al. A peptide derived from the Wiskott-Aldrich syndrome (WAS) protein- interacting protein (WIP) restores WAS protein level and actin cytoskeleton reorganization in lymphocytes from patients with WAS mutations that disrupt WIP binding. J Allergy Clin Immunol 2011; 127(4):998-1005.
5. Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, et al.Clinical course of patients with WASP gene mutations. Blood 2004; 103(2):456–64.
6. Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, et al. Mutations of the Wiskott–Aldrich syndrome protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood 2004; 104:4010–9.
7. Jones LN, Lutskiy MI, Cooley J, Kenney DM, Rosen FS, Remold-O'Donnell EA. Novel Protocol to Identify Mutations in Patients with Wiskott–Aldrich Syndrome. Blood Cells Mol Dis 2002; 28, (3): 392-8.
8. Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott–Aldrich syndrome. Cell 1994;78(4):635–44.
9. Finan PM, Soames CJ, Wilson L, Nelson DL, Stewart DM, Truong O, et al. Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains. J Biol Chem 1996; 271(42):26291-5.
10. Thompson LJ, Lalloz MRA, Layton DM. Unique and Recurrent WAS Gene Mutations in Wiskott - Aldrich syndrome and X-Linked Thrombocytopenia. Blood Cells Mol Dis 1999; 25(3-4):218-26.
11. Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, Mccormick F, et al. Wiskott- Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 1996; 84(5):723–34.
12. Burns S, Cory GO, Vainchenker W, Thrasher AJ.Mechanisms of WASP-mediated hematologic and immunologic disease. Blood 2004; 104(12):3454–62.
13. Sasahara Y, Rachid R, Byrne MJ, de la Fuente MA,Abraham RT, Ramesh N, et al. Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation. Mol Cell 2002;10(6):1269–81.
14. Luthi JN, Gandhi MJ, Drachman JG. X-linked thrombocytopenia caused by a mutation in the Wiskott– Aldrich syndrome (WAS) gene that disrupts interaction with the WAS protein (WASP) - interacting protein (WIP). Exp Hematol 2003; 31(2):150–8.
15. Konno A, Kirby M, Anderson SA, Schwartzberg PL, Candotti F. The expression of Wiskott–Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP). Int Immunol 2007; 19(2):185–92.
16. Hwang DJ, Yang JW, Kim SY, Yi HK, Lee DY, Hwang PH. Diagnostic Approach of Wiskott - Aldrich syndrome. Korean J Pediatr 2004; 47(7):726-34.
17. Rong, S.B, Vihinen, M. Structural basis of Wiskott- Aldrich syndrome causing mutations in the WH1 domain. J Mol Med 2000; 78(9):530–7.

Files
IssueVol 11, No 4 (2012) QRcode
SectionArticles
Keywords
Mutations Thrombocytopenia Wiskott-Aldrich syndrome
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Safaei S, Fazlollahi MR, Houshmand M, Hamidieh AA, Bemanian MH, Alavi S, Mousavi F, Pourpak Z, Moin M. Detection of Six Novel Mutations in WASP Gene in Fifteen Iranian Wiskott-Aldrich Patients. Iran J Allergy Asthma Immunol. 1;11(4):345-348.