Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients

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Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients Xian Qin, Li-Ping Jiang, Xue-Mei Tang, Mo Wang, En-Mei Liu, Xiao-Dong Zhao Chongqing, China

Methods: Twenty children with XLA-compatible phenotypes from 18 unrelated families were enrolled in this study. The BTK gene was amplified and sequenced, followed by mutation analysis in these children and their female relatives. Results: Eighteen different mutations of the BTK gene were identified in the 20 patients. Eleven mutations had been reported previously including eight missense mutations (c.994C>T, c.1987C>A, c.1885G>T, c.502T>C, c.1085C>T, c.1816C>T, c.214C>T, c.1912G>A) and three nonsense mutations (c.1267T>A, c.1793C>G, c.1618C>T). Seven novel mutations of the BTK gene were also presented and included five missense mutations (c.134T>A, c.1646T>A, c.1829C>G, c.711G>T, c.1235G>A), one splice-site mutation (c.523+1G>A) and one insertion mutation (c.1024-1025in sTTGCTAAAGCAACTGCTAAAGCAAG). Eight out of 18 mutations of the BTK gene were located in the TK domain, 4 in the PH domain, 4 in the SH2 domain and 2 in the TH domain. Genetic study for carrier status was carried out in 18 families with definite BTK gene

Author Affiliations: Division of Immunology, Children's Hospital of Chongqing Medical University; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics, Committee of Science and Technology in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China (Qin X, Jiang LP, Tang XM, Wang M, Liu EM, Zhao XD) Corresponding Author: Xiao-Dong Zhao, MD, PhD, Division of Immunology, Children's Hospital, Chongqing Medical University, Chongqing 400014, China (Tel: 86 23 6362 2554; Fax: 86 23 6360 2136; Email: [email protected]) doi: 10.1007/s12519-013-0400-x ©Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2013. All rights reserved.

World J Pediatr, Vol 9 No 3 . August 15, 2013 . www.wjpch.com

mutations. Nine carriers with BTK gene mutations were identified. Six families without carriers were detected, and 3 patients were not tested in this study. Conclusion: Our results support that molecular genetic testing represents an important tool for early confirmed diagnosis of congenital agammaglobulinemia and may allow accurate carrier detection and prenatal diagnosis. World J Pediatr 2013;9(3):273-277 Key words: BTK gene; genotype-phenotype correlation; mutations; X-linked agammaglobulinemia

Introduction

X

-linked agammaglobulinemia (XLA, MIM# 300300) is a prototypical humoral immunodeficiency disease. In 1952, Bruton[1] described the first case of XLA in a male patient with recurrent bacterial infections. XLA is the most common form of inherited antibody deficiency disorder and is characterized by markedly reduced serum levels of all major classes of immunoglobulins and few or no mature circulating B cells.[2] Affected individuals have markedly