Mutation of the <Emphasis Type="Italic">BTK</Emphasis> Gene and Clinical Feature of X-Linked Agammaglobulinemia in Mainland China |
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Authors: | Ying Wang Hirokazu Kanegane Xiaochuan Wang Xiaohua Han Qian Zhang Shunying Zhao Yeheng Yu Jingyi Wang and Toshio Miyawaki |
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Institution: | (1) Department of Clinical Immunology, Jeffrey Modell Diagnostic and Research Center, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China;(2) Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Japan;(3) Department of Pediatrics, Shengjing Hospital, China Medical University, Shenyang, China;(4) Beijing Children’s Hospital Affiliated to Capital University of Medical Sciences, Beijing, China |
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Abstract: | Introduction X-Linked agammaglobulinemia is a prototypical humoral immunodeficiency with the mutation of the Bruton’s tyrosine kinase gene.
Methods We investigated the gene mutation and clinical features of 30 Chinese X-linked agammaglobulinemia (XLA) patients from 27 families.
There were 26 mutations, including 11 novel and 15 recurrent mutations, distributing over the entire gene. The nucleotide
and amino acid aberration, 1129C>T(H333Y) and 1196T>A(I355N), in SH2 have not been reported before. Five (I355N, W124R, R520X,
I590F, G594E) of the 24 mutations not detected in the mothers receiving gene analysis were determined to be de novo. Two mutations
occurred within intronic splice-site sequences (intron5(−2)A>G, intron17(−2)A>T).
Results and Discussion There are eight mutations in the PH domain, two mutations in the SH3 domain, three mutations in the SH2 domain, one mutation
in the TH domain, and other 16 mutations in the TK domain. The mutations of protein domain is most common in TK (53%) domain
and then in PH(8%) domain. Missense and nonsense mutations were found equal in 46% of the detected mutations. All of the patients
are alive, but one died of liver cancer. Clinical features and serum Igs levels range variedly and were not correlated with
genotypes. Our results demonstrated molecular genetic characteristics of XLA in mainland China. |
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Keywords: | Humoral immunodeficiency X-linked agammaglobulinemia mutation Bruton’ s tyrosine kinase |
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