Clinical features and molecular analysis often patients with Wiskott-Aldrich syndrome in China

XIAO Huiqin; ZHANG Zhiyong; JIANG Liping; YU Jie; YANG Xiqiang; ZHAO Xiaodong

Abstract：To explore the clinical and molecular features of ten Chinese patients with Wiskott-Aldrich syndrome (WAS).Clinical data of ten boy patients was analyzed, including clinical manifestations, scoring of the phenotype, peripheral blood, immunological functions, bone marrow examination, and scanning electron microscope (SEM).And then, flow cytometry was used to analyze the WAS protein (WASP) expression in peripheral blood mononuclear cells (PBMCs) of ten patients; PCR direct sequence analysis of WASP gene was performed in nine unrelated Chinese families.Most patients had hematorrhea and petechiae as initial symptom in early lifetime; all ten patients presented as classic WAS phenotype, while none had the X-linked thrombocytopenia (XLT) phenotype.Three patients scored 5 had autoimmune dis-orders or tumor, including autoimmune hemolysis (AIHA) in two patients and retinoblastoma in one patient.Three patients scored 4 due to severe eczema and infections, while the other four patients scored 3.All patients had the presentation of persistent thrombocytopenia, de-creased mean platelet volume (MPV), among them, four patients had eosinophilia.Most patients showed elevated IgA (8/9), IgE (8/9), and IgG (7/9).Six patients showed decreased CD4+ T lymphocyte (6/9).Five WAS patients had typical SEM anomalies on lymphocytes.Defi-cient WASP expressions were exclusively demonstrated in all patients.Nine of the ten patients had 7 different mutations including 4 non-sense mutations (155 C>T, R 41 X in 2 cases; 665 C>T,R 211 X in 2 cases), 2 missense mutation (168 C>A, T 45 K~*;1487G>A, D485N/5' splice site), a deletion mutation (747-748 del T, 1238 Fs X260~*), a splice anomaly (Ivs9 +2 T>C), and a insertion mutation (253 Ins A, C73X~*).Three novel mutations were identified and marked with asterisk (*); four of seven mutations located in EVH1.Eight of nine mothers were analyzed and all of them were carriers.Three patients received hematopoietic stem cell transplantation (HSCT) and one died from cytomegalovirus pneumonitis.All results suggest that male patients, presenting with hematorrhea and early-onset thrombocytope-nia associated with small MPV, should be suspected of WAS.Flow cytometric analysis of the WASP expression in PBMC and further WASP gene sequence analysis are the keys to prompt diagnosis and finding of carriers.HSCT is currently the mainstay of treatment for WAS, especial-ly those with classic WAS phenotype.