Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China

Ying Wang, Hirokazu Kanegane, Xiaochuan Wang, Xiaohua Han, Qian Zhang, Shunying Zhao, Yeheng Yu, Jingyi Wang, Toshio Miyawaki

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)352-356
Number of pages5
JournalJournal of Clinical Immunology
Volume29
Issue number3
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Fingerprint

China
Mutation
Genes
src Homology Domains
Bruton type agammaglobulinemia
Nonsense Codon
Missense Mutation
Liver Neoplasms
Molecular Biology
Nucleotides
Genotype
Mothers
Amino Acids

Keywords

  • Bruton's tyrosine kinase
  • Humoral immunodeficiency
  • Mutation
  • X-linked agammaglobulinemia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China. / Wang, Ying; Kanegane, Hirokazu; Wang, Xiaochuan; Han, Xiaohua; Zhang, Qian; Zhao, Shunying; Yu, Yeheng; Wang, Jingyi; Miyawaki, Toshio.

In: Journal of Clinical Immunology, Vol. 29, No. 3, 05.2009, p. 352-356.

Research output: Contribution to journalArticle

Wang, Y, Kanegane, H, Wang, X, Han, X, Zhang, Q, Zhao, S, Yu, Y, Wang, J & Miyawaki, T 2009, 'Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China', Journal of Clinical Immunology, vol. 29, no. 3, pp. 352-356. https://doi.org/10.1007/s10875-008-9262-8
Wang, Ying ; Kanegane, Hirokazu ; Wang, Xiaochuan ; Han, Xiaohua ; Zhang, Qian ; Zhao, Shunying ; Yu, Yeheng ; Wang, Jingyi ; Miyawaki, Toshio. / Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China. In: Journal of Clinical Immunology. 2009 ; Vol. 29, No. 3. pp. 352-356.
@article{b319f433810c400eae6c968c7e70393a,
title = "Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China",
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.",
keywords = "Bruton's tyrosine kinase, Humoral immunodeficiency, Mutation, X-linked agammaglobulinemia",
author = "Ying Wang and Hirokazu Kanegane and Xiaochuan Wang and Xiaohua Han and Qian Zhang and Shunying Zhao and Yeheng Yu and Jingyi Wang and Toshio Miyawaki",
year = "2009",
month = "5",
doi = "10.1007/s10875-008-9262-8",
language = "English",
volume = "29",
pages = "352--356",
journal = "Journal of Clinical Immunology",
issn = "0271-9142",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China

AU - Wang, Ying

AU - Kanegane, Hirokazu

AU - Wang, Xiaochuan

AU - Han, Xiaohua

AU - Zhang, Qian

AU - Zhao, Shunying

AU - Yu, Yeheng

AU - Wang, Jingyi

AU - Miyawaki, Toshio

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

KW - Bruton's tyrosine kinase

KW - Humoral immunodeficiency

KW - Mutation

KW - X-linked agammaglobulinemia

UR - http://www.scopus.com/inward/record.url?scp=67349160500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349160500&partnerID=8YFLogxK

U2 - 10.1007/s10875-008-9262-8

DO - 10.1007/s10875-008-9262-8

M3 - Article

VL - 29

SP - 352

EP - 356

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

SN - 0271-9142

IS - 3

ER -