Clinical and genetic analysis of 10 cases with X-linked agammaglobulinemia

ZHANG Zhiyong; ZHAO Xiaodong; WANG Mo; JIANG Liping; CUI Yuxia; ZHAO Yao; AN Yunfei; YANG Xiqiang

Abstract：Objective To realize the feature of gene mutation of X-linked agammaglobulinemia(XLA)in Chinese children.Methods Ten patients from 10 unrelated Chinese families were included in the study.All patients were male and diagnosed as having XLA.The diagnosis of XLA was based on the absence or very low levels of B cells in the blood,low levels of immunoglobulins and a history of recurrent bacterial infections.To identify mutations in the coding region of(Bruton's tyrosine kinase)BTK,cDNA was prepared by a reverse transcriptase PCR reaction from peripheral blood mononuclear cells.The amplified products were directly sequenced by cycle sequencing.The detected mutation was confirmed on genomic DNA templates.Results Seven different mutations were identified in the 7 patients and no mutation was found in the other 3 patients.Six mutations located at BTK coding region and one mutation located at splice site.The types of mutation included three missense mutations,one nonsense mutation,two deletion mutations,and a splice site mutation.Five of the seven mutations(F583L,135Nfs177X,R123X,C502Y,IVS9+2T＞C)are novel mutation types which have not been reported.The spot mutation in splice site of intron 9 (IVS9+2T＞C)resulted in exon 9 skipping.Six of seven mothers were analyzed and all of them were carriers.Conclusion The results of this study further support the notion that molecular genetic testing represents an important tool for definitive and early diagnosis of XLA and may allow accurate carrier detection and prenatal diagnosis.Those patients without mutation identified in the BTK gene may require a further genetic analysis on autosomal recessive bases.