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The first part of the 24 cases of Wiskott-Aldrich syndrome children with genotype and clinical phenotype relationship analysis purposes: preliminary analysis of the relationship between genotype and clinical phenotype of 24 cases of Wiskott-Aldrich syndrome (WAS) in children. : April 2009 to November 2010, collected 24 cases of of WAS children with clinical data, clinical phenotype score. Flow cytometry (FCM) was used to detect the expression of peripheral blood mononuclear cells (PBMCs) WAS protein (WASP). WASP gene by direct sequencing and analysis of the relationship between genotype and phenotype. Results: 24 patients were all male, two cases of clinical phenotype score 2 points, for the rest of the X chain thrombocytopenia (XLT); children score ≥ 3 points, for the typical WAS. In addition the one cases WASP normal expression, one case of WASP expression reduced, the remaining children the WASP are all negative. Found that the WASP gene mutations, including seven missense mutations, three cases of nonsense mutations, seven cases of deletion mutations, and 7 patients with splice site mutations. A total of 21 kinds of genetic mutation, new mutation of three kinds, namely 180 C gt; T (A49V) of ,342-343del CA (S103fsX121) 2 T IVS7, gt; C Found six kinds of hotspot mutations have been reported, including 291 G gt; A (R86H), 291G gt; T (R86L) 1035del of G (G334fsX444), 665 C gt; T (R211X), IVS6 G gt; A, IVS8 1 G gt; A. Two cases of children with missense mutations the XLT, of the rest are typical WAS. Nonsense mutations, children are rated 3 to 5 typical WAS deletion mutations and splice site mutations, some children with severe phenotype. Conclusion: missense mutation phenotype in children with multiple foreign scholars reported, the reason is not clear. WASP downstream region of the gene mutation, nonsense, deletions, splice site mutation type is more likely to lead to WASP expression loss of unstable or the truncated WASP, clinical phenotype typical WAS. The effect of environmental factors on the performance of children with type should not be underestimated, and can lead to aggravation of phenotype in children. The second part of one cases of the WASP spontaneous reply mutations in children between genotype and phenotype relationship to explore Objective: Analysis 1 cases WASP revertant Wiskott-Aldrich syndrome children with genotype and clinical phenotype relationship. Methods: WAS children clinical data, clinical phenotype score. Flow cytometry (FCM) was used to detect expression of peripheral blood mononuclear cells (PBMCs) WAS protein (WASP). Of WASP gene sequence analysis, and analysis of the genotype, analysis of the relationship between genotype and phenotype after cloning its cDNA line TA. Results: The children of 12-year-old male, clinical phenotype score was reduced to 2 points by early disease, in addition to platelets still less, children from the age of 10 after the eczema disappeared, not life-threatening infections and bleeding events occurred. PBMCs part of the expression of WASP, the primary mutation exon1 155 C gt; T, WASP at the termination of the first 41 amino acids encoded (R41X), and his mother for the primary mutation carriers. TA cloning children cDNA, and found that 85% (17/20) of the clones showed primary 155C gt; T mutation, the remaining 15% (3/20) of the clones in the 155 for the base C is normal gene type. Conclusion: WASP mutation may lead to children an important part of the immune cell function reconstruction, so that the clinical improvement in its performance, but the reverse mutation mechanism and its impact on the long-term prognosis is unclear.
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