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Clinical Characteristics and Genotype-phenotype Correlation in 62 Patients with X-linked Agammaglobulinemia

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Abstract

Introduction

X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Bruton's tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in XLA, but a definitive association remains controversial.

Patients and Methods

We examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis.

Results

Fifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections.

Conclusion

A critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.

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Acknowledgment

The authors would like to thank the Hong Kong Society for the Relief of Disabled Children for funding the molecular testing of primary immunodeficiency disorders for our patients.

Conflict of Interest

All the authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China

    Pamela P. W. Lee, Koon-Wing Chan, Wanling Yang, Susanna F. S. Fok, Tsz-Leung Lee, Marco H. K. Ho & Yu-Lung Lau

  2. Department of Pediatrics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Tong-Xin Chen

  3. Chongqing Children’s Hospital, Chongqing University of Medical Sciences, Chongqing, China

    Xi-Qiang Yang

  4. Department of Paediatrics, National University of Singapore, Singapore, Singapore

    Bee-Wah Lee

  5. Department of Paediatric Medicine, Kandang Kerbau Women’s and Children’s Hospital, Singapore, Singapore

    Wen-Chin Chiang

  6. Immunology Department, Guangzhou Children’s Hospital, Guangzhou, China

    Xiang-Yuan Chen

  7. Children’s Hospital of Chongqing Medical University, Chongqing, China

    Li-Ping Jiang

Authors
  1. Pamela P. W. Lee
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  2. Tong-Xin Chen
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  3. Li-Ping Jiang
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  4. Koon-Wing Chan
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  5. Wanling Yang
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  6. Bee-Wah Lee
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  7. Wen-Chin Chiang
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  8. Xiang-Yuan Chen
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  9. Susanna F. S. Fok
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  10. Tsz-Leung Lee
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  11. Marco H. K. Ho
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  12. Xi-Qiang Yang
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  13. Yu-Lung Lau
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Corresponding author

Correspondence to Yu-Lung Lau.

Additional information

PPW Lee and TX Chen were co-first authors and had equal contributions to the study.

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Lee, P.P.W., Chen, TX., Jiang, LP. et al. Clinical Characteristics and Genotype-phenotype Correlation in 62 Patients with X-linked Agammaglobulinemia. J Clin Immunol 30, 121–131 (2010). https://doi.org/10.1007/s10875-009-9341-5

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  • DOI: https://doi.org/10.1007/s10875-009-9341-5

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