Case Report
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 6, 2020; 8(17): 3859-3866
Published online Sep 6, 2020. doi: 10.12998/wjcc.v8.i17.3859
Novel deletion mutation in Bruton’s tyrosine kinase results in X-linked agammaglobulinemia: A case report
Xiao-Mei Hu, Ke Yuan, Hong Chen, Chun Chen, Yan-Lan Fang, Jian-Fang Zhu, Li Liang, Chun-Lin Wang
Xiao-Mei Hu, Ke Yuan, Hong Chen, Chun Chen, Yan-Lan Fang, Jian-Fang Zhu, Li Liang, Chun-Lin Wang, Department of Pediatrics, The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Hu XM and Wang CL conceived and designed the study; Yuan K, Hu XM, Chen H, and Fang YL performed the experiments; Chen C and Zhu JF provided clinical research; Hu XM wrote the paper; Hu XM, Yuan K, Liang L and Wang CL reviewed and edited the manuscript; all authors read and approved the manuscript.
Supported by National Natural Science Foundation of China, No. 11571309; and the Zhejiang Health Bureau Fund, No. 2016ZHA004.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this manuscript.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Chun-Lin Wang, PhD, Chief Doctor, Department of Pediatrics, The First Affiliated Hospital of Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. hzwangcl@zju.edu.cn
Received: March 3, 2020
Peer-review started: March 3, 2020
First decision: April 28, 2020
Revised: July 8, 2020
Accepted: July 18, 2020
Article in press: July 18, 2020
Published online: September 6, 2020
Processing time: 185 Days and 2.6 Hours
Abstract
BACKGROUND

X-linked agammaglobulinemia is a primary immunodeficiency disease caused by gene mutations of Bruton’s tyrosine kinase (BTK). We found a new mutation point and summarized the correlation analysis and performed a literature review.

CASE SUMMARY

The proband was a 5-year-old boy. He was admitted to our hospital due to a recurrent cough and a fever that had persisted for a month. He had a history of multiple respiratory infections and sinusitis. There was no immunodeficiency or recurrent infection history among his family members. Agammaglobulinemia was characterized as follows: Immunoglobulin (Ig) A, 90.0 mg/dL (90-450 mg/dL); IgG, 20.0 mg/dL (800-1800 mg/dL); and IgM, 18.0 mg/dL (60-280 mg/dL). Notably, the assessment of IgG subtypes revealed the following very low levels: Subtype 1, 0.26 g/L (3.62-12.28 g/L); subtype 2, 0.10 g/L (0.57-2.9 g/L); subtype 3, 0.009 g/L (0.129-0.789 g/L); and subtype 4, 0.003 g/L (0.013-1.446 g/L). Cellular immunological test results were as follows: CD3, 74.6% (50%-84.0%); CD4, 47.3% (27.0%-51.0%); and CD8, 24.9% (15.0%-44.0%). A de novo hemizygous deletion in BTK was detected: c.902_c.904delAAG/p.E301del. Transcript levels of the mutant BTK were similar to those of the wild-type gene, though overexpression resulted in markedly reduced levels of mutant BTK (9.49% ± 1.58%), relative to the wild-type BTK (75.8% ± 2.98%, P < 0.01).

CONCLUSION

This case of X-linked agammaglobulinemia was attributed to a de novo hemizygous deletion mutation in BTK (c.902_c.904delAAG/p.E301del). The mutation resulted in markedly reduced BTK protein stability in vitro.

Keywords: Agammaglobulinemia, Bruton’s tyrosine kinase, Mutation, Immunodeficiency, Case report

Core tip: This report introduces the diagnosis and treatment of X-linked agammaglobulinemia caused by a new Bruton’s tyrosine kinase gene mutation, and includes a detailed clinical and laboratory analysis of its pathogenic principle, which provided the diagnosis and led to the treatment of X-linked agammaglobulinemia.