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Damaging BTK Variant Demonstrated by Carrier, Allele-Specific BTK Expression in B Cells and Monocytes

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Abbreviations

BTK:

Bruton’s tyrosine kinase

FACS:

Fluorescence activated cell sorting

NGS:

Next generation sequencing

VUS:

Variant of uncertain significance

XLA:

X-linked agammaglobulinemia

References

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Acknowledgements

We thank Emma Cook for her editorial expertise and Erin Hammelev for IRB assistance.

Author information

Author notes

  1. James Verbsky and John Routes contributed equally to this work.

Authors and Affiliations

  1. Division of Asthma, Allergy and Clinical Immunology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Mary T. Bausch-Jurken, Jeffrey Woodliff, Amy Rymaszewski & John Routes

  2. Asthma, Allergy and Clinical Immunology, Children’s Hospital of Wisconsin, Milwaukee, WI, USA

    Mary Hintermeyer

  3. Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Shaoying Chen & James Verbsky

  4. Department of Pediatrics, Children’s Hospital of Wisconsin, Medical College of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI, 53226-4874, USA

    John Routes

Authors
  1. Mary T. Bausch-Jurken
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  2. Mary Hintermeyer
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  3. Jeffrey Woodliff
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  4. Shaoying Chen
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  5. Amy Rymaszewski
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  6. James Verbsky
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  7. John Routes
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Corresponding author

Correspondence to John Routes.

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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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Electronic supplementary material

ESM 1

(DOCX 18 kb)

Supplementary Figure 1

A. Position of the variant in BTK (c. 1004T>A) (top) and with p.V335D mutation in the protein (bottom). Primers for RT-PCR cDNA amplification are highlighted in yellow, with the nucleotide substitution indicated in red. PH, pleckstrin homology; TH, TEC homology domain; SH, src homology. B. Outline of the FACS and RNA sequencing of B cells and monocytes in carrier. (PDF 96 kb)

Supplementary Figure 2

Flow cytometry histograms measuring BTK expression in the proband and the sister. Expression was measured in CD14+ monocytes and CD19+ B cells. The isotype controls for each subject sample is presented across the top row, whereas the subject results are shown across the bottom row. Quantification of the expression is included in Table 1. (PDF 54 kb)

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Bausch-Jurken, M.T., Hintermeyer, M., Woodliff, J. et al. Damaging BTK Variant Demonstrated by Carrier, Allele-Specific BTK Expression in B Cells and Monocytes. J Clin Immunol 39, 23–25 (2019). https://doi.org/10.1007/s10875-019-0591-6

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  • DOI: https://doi.org/10.1007/s10875-019-0591-6

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