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Somatic hypermutation defects in two adult hyper immunoglobulin M patients

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Abstract

Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the underlying genetic variation. In this study, we identified two novel variants in AID and UNG genes, which are associated with autosomal recessive type HIGM, by targeted next-generation sequencing (NGS) panel. A biallelic 11 base pair deletion (c.278_288delATGTGGCCGAC) in the coding sequence of activation-induced cytidine deaminase (AID) gene was identified in a 36-year-old patient. Biallelic two base pair insertion in exon 7 of uracil nucleoside glycosylase (UNG) gene (c.924_925insGG) was identified in a 40-year-old patient. Both variants were confirmed by Sanger sequencing. HIGM, like many of the other primary immunodeficiencies, is a rare and difficult-to-diagnose entity with heterogeneous clinical phenotypes. It should be suspected in patients with a history of early-onset recurrent respiratory infections, enlarged lymph nodes, and autoimmune disorders. There might be a delay in diagnosis until adulthood especially in subtle cases or if HIGM is not included in the differential diagnosis due lacking of awareness. In this regard, genetic testing with NGS-based diagnostic panels provide a rapid and reasonable tool for the molecular diagnosis of patients with immunodeficiencies and hence, decrease the time to diagnose and prevent infection-related complications associated with increased morbidity and mortality.

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Funding

This project is supported by Istanbul University Research Fund with the project numbers: TYO-2017–24271 and TTU-2016–21237.

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Authors and Affiliations

  1. Hematology Department, Faculty of Medicine, Ankara University, Ankara, Turkey

    Hülya Yilmaz

  2. Bioinformatics and Genetics Department, Engineering and Natural Sciences Faculty, Istinye University, Istanbul, Turkey

    Sinem Fırtına

  3. Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey

    Merve Sarıtaş

  4. Aziz Sancar Institute of Experimental Medicine Genetics Department, Istanbul University, Istanbul, Turkey

    Müge Sayitoğlu

  5. Hematology Department, Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa, Istanbul, Turkey

    Muhlis Cem Ar

Authors
  1. Hülya Yilmaz
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  2. Sinem Fırtına
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  3. Merve Sarıtaş
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  4. Müge Sayitoğlu
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  5. Muhlis Cem Ar
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Contributions

Yilmaz, H.; Fırtına, S.; Ar, M. C.; Sayitoğlu, M.; and Sarıtaş, M., designed the research; Ar, M.C.; Yilmaz, H.; Sayitoğlu, M.; Fırtına, S.; and Sarıtaş, M., conducted the review and editing; Ar, M. C., and Yilmaz, H., provided funding acquisition, project administration, and resources; Ar, M. C.; Yilmaz, H.; Sayitoğlu, M.; and Fırtına, S., wrote the paper.

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Correspondence to Hülya Yilmaz.

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All procedures performed in studies involving human participants followed the institutional research committee’s ethical standards and the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The patients consent to the use of their clinical information to the redaction of this study.

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The patients formally consented to the use of their clinical information to be published for this study.

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The authors declare no competing interests.

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Yilmaz, H., Fırtına, S., Sarıtaş, M. et al. Somatic hypermutation defects in two adult hyper immunoglobulin M patients. Immunol Res 70, 811–816 (2022). https://doi.org/10.1007/s12026-022-09310-y

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  • DOI: https://doi.org/10.1007/s12026-022-09310-y

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