Abstract：OBJECTIVE: This study investigated the history and gene mutations of a family with X-linked thrombocytopenia, in order to understand the clinical characteristic and molecular pathogenesis of the disease. METHODS: A three-generation X-linked thrombocytopenia family with 13 family members was investigated using PCR-DNA direct sequencing method to screen the exons of WASP gene for mutation analysis. RESULTS: The WASP gene sequencing of the proband revealed a missense mutation in exon 2 (G291A), resulting in a change of amino acid 86 from arginine to histidine. The patient′s mother was the carrier of the heterozygosis mutation in X-chromosome. CONCLUSIONS: WASP mutations may be attributed to the molecular mechanism of X-linked thrombocytopenia. G291A is one of the mutations of WASP.［Chin J Contemp Pediatr, 2010, 12 (10):784-787］
［1］Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene［J］. Nat Genet, 1995, 9(4):414-417.
［2］Thompson LJ, Lalloz MR, Layton DM. Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia［J］. Blood Cells Mol Dis, 1999, 25(3-4):218-226.
［3］Ochs HD, Thrasher AJ. The Wiskott-Aldrich syndrome［J］. J Allergy Clin Immunol, 2006,117(4):725-738.
［4］Remold-O′Donnell E, Rosen FS, Kenney DM. Defects in Wiskott-Aldrich syndrome blood cells［J］.Blood，1996，87(7)：2621-2631.
［5］Park JY, Shcherbina A, Rosen FS, Prodeus AP, Remold-O′Donnell E. Phenotypic perturbation of B cells in the Wiskott-Aldrich syndrome［J］. Clin Exp Immunol, 2005, 139(2):297-305.
［6］Gallego MD, de la Fuente MA, Anton IM, Snapper S, Fuhlbrigge R, Geha RS. WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1alpha［J］. Int Immunol, 2006, 18(2):221-232.
［7］Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, et al. Clinical course of patients with WASP gene mutations［J］. Blood, 2004,103(2):456-464.
［8］Millard TH, Sharp SJ, Machesky LM. Signalling to actin assembly via the WASP-family protein and the Arp2/3 complex［J］. J Biochem, 2004, 38(1):1-17.
［9］Notarangelo LD, Notarangelo LD, Ochs HD. WASP and the phenotypic range associated with deficiency［J］.Curr Opin Allergy Clin Immunol, 2005, 5(6):485-490.
［10］Proust A, Guillet B, Picard C, de Saint Basile G, Pondarré C, Tamary H, et al. Detection of 28 novel mutations in the Wiskott-Aldrich syndrome and X-linked thrombocytopenia based on multiplex PCR［J］. Blood Cells Mol Dis, 2007, 39(1):102-106.
［11］Andreu N, Pujol-Moix N, Martinez-Lostao L, Oset M, Muniz-Diaz E, Estivill X, et al. Wiskott-Aldrich syndrome in a female with skewed X-chromosome inactivation［J］. Blood Cells Mol Dis, 2003, 31(3):332-337.
［12］De la Fuente MA, Sasahara Y, Calamito M, Antón IM, Elkhal A, Gallego MD, et al. WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP)［J］. Proc Natl Acad Sci USA, 2007, 104(3):926-931.
［13］Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N. Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment［J］. Biol Blood Marrow Transplant, 2009, 15(1):84-90.
