BTKbase: the mutation database for X-linked agammaglobulinemia.

Area of Science:

• Genetics
• Immunology
• Bioinformatics

Background:

• X-linked agammaglobulinemia (XLA) is a primary immunodeficiency.
• It results from mutations in the Bruton tyrosine kinase (BTK) gene.
• XLA patients exhibit reduced mature B cells and immunoglobulin production, leading to recurrent bacterial infections.

Purpose of the Study:

• To present BTKbase version 8, a comprehensive database of XLA-causing mutations.
• To analyze the characteristics and distribution of these mutations.
• To provide a resource for understanding BTK mutations in XLA.

Main Methods:

• Data compilation from patients with XLA-causing BTK mutations.
• Utilizing the MUTbase program suite for data management and submission.
• Analysis of mutation localization, frequency, and structural/functional impact.

Main Results:

• BTKbase version 8 includes 602 unique mutations from 1,111 patients across 973 families.
• Mutations are distributed across BTK domains, with notable exceptions.
• CpG dinucleotides are frequent mutation sites, and missense mutations often disrupt protein folding or stability.

Conclusions:

• BTKbase serves as a valuable, curated resource for XLA research.
• Mutation analysis reveals patterns in affected sites and structural consequences.
• Understanding these mutations is crucial for diagnosing and potentially treating XLA.