Novel Deletion Mutation in Bruton’s Tyrosine Kinase Results in X-linked Agammaglobulinemia: A Case Report

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%). Ade novohemizygous deletion inBTKwas detected: c.902_c.904delAAG/p.E301del. Transcript levels of the mutantBTKwere similar to those of the wild-type gene, though overexpression resulted in markedly reduced levels of mutantBTK(9.49% +/- 1.58%), relative to the wild-typeBTK(75.8% +/- 2.98%, P < 0.01). CONCLUSION This case of X-linked agammaglobulinemia was attributed to ade novohemizygous deletion mutation inBTK(c.902_c.904delAAG/p.E301del). The mutation resulted in markedly reducedBTKprotein stabilityin vitro.