A novel deletion mutation and structural abnormality in the Bruton's tyrosine kinase gene identified in a Chinese patient with X-linked agammaglobulinemia

• Published in: Clinical laboratory (Heidelberg) Vol. 60; no. 5; p. 859
• Main Authors: Wang, Shifu, Lu, Yanqin, Li, Hu, Wang, Zhaoxia, Mo, Xinkai, Chai, Zhengbin, Han, Jinxiang
• Format: Journal Article
• Language: English
• Published: Germany 2014
• Subjects: Agammaglobulinemia - genetics; Child, Preschool; China; Codon, Nonsense; Frameshift Mutation; Genetic Diseases, X-Linked - genetics; Humans; Male; Protein Conformation; Protein-Tyrosine Kinases - genetics; Sequence Deletion; China
• ISSN: 1433-6510
• DOI: 10.7754/Clin.Lab.2013.130631

X-linked agammaglobulinemia (XLA) is a heritable primary immune deficiency disorder caused by mutation of Bruton's tyrosine kinase (BTK) gene. The main clinical characteristics of XLA are recurrent respiratory tract infections and profoundly low serum immunoglobulin levels and B cells. The clinical characteristics of a five-year-old Chinese boy with XLA were described. Mutations of BTK genes were identified by traditional DNA sequencing based on PCR. A three-dimensional model of the truncated BTK protein was constructed. Molecular analysis showed a point deletion of an adenine nucleotide at position 1427 (p.Tyr476Ser), which would cause a frameshift and premature termination at codon 484. Three-dimensional analysis showed that the truncated protein had lost the functional region for both ATP and substrate binding such that tyrosine kinase activity would be affected. The study identified a novel BTK mutation of one Chinese XLA patient. The truncated BTK model identified the loss of a functional domain.