Damaging BTK Variant Demonstrated by Carrier, Allele-Specific BTK Expression in B Cells and Monocytes
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To the Editor:
With the increased use of next generation sequencing (NGS), ascertaining the clinical significance of a variant of unknown significance (VUS) is a difficult and common problem. In silico protein modeling and pathway analysis is currently not definitive, and in vitro or in vivo evaluation of the function of the mutant protein can be challenging, expensive and time consuming. We report a novel approach to define the pathogenicity of a VUS in the BTK gene that led to the diagnosis of XLA. This approach may be useful in defining the pathogenicity of VUS in other X-linked disorders.
KeywordsX-linked agammaglobulinemia Bruton’s tyrosine kinase
Bruton’s tyrosine kinase
Fluorescence activated cell sorting
Next generation sequencing
Variant of uncertain significance
We thank Emma Cook for her editorial expertise and Erin Hammelev for IRB assistance.
Compliance with Ethical Standards
Conflict of Interest
Dr. Routes reports a grant and independent contractor from CSL Behring, a grant from Baxalta, grant from Bio Products Laboratory Limited, outside the submitted work. All other authors declare that they have no conflict of interest.
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