Abstract
Purpose
Determining the monogenic cause of antibody deficiency and immune dysregulation in a non-consanguineous family with healthy parents, two affected children, and one unaffected child.
Methods
Whole Exome Sequencing (WES) was performed in the index family. WES results were confirmed by Sanger Sequencing. Dried plasma spots of the male patient and his mother were analyzed for ADA2 enzymatic activity.
Results
Following data analysis of WES, we found a compound heterozygous mutation in CECR1 (encoding adenosine deaminase 2, ADA2) that segregated in the two affected children. Enzyme activity measurement confirmed a severely diminished ADA2 activity in our patient. The 32 year old index patient was suffering from recurrent respiratory infections and was previously diagnosed with common variable immunodeficiency (CVID), showing no signs of vasculitis. His sister had a systemic lupus erythematosus (SLE)-like phenotype and died at age 17.
Conclusions
Deficiency of ADA2 (DADA2) has been reported to cause vasculopathy and early-onset stroke. Our case suggests that it should also be considered when evaluating patients with antibody deficiencies and immune dysregulation syndromes.
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Acknowledgments
The financial support for the conduct of the research came from the German Ministry of Education and Research (BMBF; grants IFB/CCI: 01E01303 and E:med SYSinflame: 01ZX1306F) and the graduate school of the medical faculty Freiburg (MOTIVATE). None of them had any role in study design, the collection, analysis and interpretation of data, the writing of the report, nor in the decision to submit the paper for publication. The authors are responsible for the content of this research.
Our dear collaborator Dr. Wilma Mannhardt-Laakman died in December 2015. We want to thank her for her dedication to caring for this family and so many other children with rheumatological and immunological conditions. We would like to dedicate this publication to her.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Wilma Mannhardt-Laakmann deceased.
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Schepp, J., Bulashevska, A., Mannhardt-Laakmann, W. et al. Deficiency of Adenosine Deaminase 2 Causes Antibody Deficiency. J Clin Immunol 36, 179–186 (2016). https://doi.org/10.1007/s10875-016-0245-x
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DOI: https://doi.org/10.1007/s10875-016-0245-x