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A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1

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Abstract

Autoimmune polyendocrine syndrome type 1 (APS-1, OMIM 2403000) is a rare autosomal recessive disease that is caused by autoimmune regulator (AIRE). The main symptoms of APS-1 are chronic mucocutaneous candidiasis, autoimmune adrenocortical insufficiency (Addison’s disease) and hypoparathyroidism. We collected APS-1 cases and analysed them. The AIRE genes of the patient and his family members were sequenced to identify whether the APS-1 patient had an AIRE mutation. We discovered a mutation site (c.206A>C) that had never before been reported in the AIRE gene located in exon 2 of the AIRE gene. This homogyzous mutation caused a substitution of the 69th amino acid of the AIRE protein from glutamine to proline (p.Q69P). A yeast two-hybrid assay, which was used to analyse the homodimerization properties of the mutant AIRE protein, showed that the mutant AIRE protein could not interact with the normal AIRE protein. Flow cytometry and RT-qPCR analyses indicated that the new mutation site could decrease the expression levels of the AIRE, glutamic acid decarboxylase 65 (GAD65) and tryptophan hydroxylase-1 (TPH1) proteins to affect central immune tolerance. In conclusion, our research has shown that the new mutation site (c.206A>C) may influence the homodimerization and expression levels and other aspects of the AIRE protein. It may also impact the expression levels of tissue-restricted antigens (TRAs), leading to a series of autoimmune diseases.

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Author notes

  1. Wufei Zhu and Zhen Hu contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, China Three Gorges University & Yichang Central People’s Hospital, Yi Ling Road 181, Yichang, 443003, China

    Wufei Zhu, Zhen Hu, Xiangyu Liao, Xing Chen, Wenrong Huang, Yu Zhong & Zhaoyang Zeng

Authors
  1. Wufei Zhu
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  2. Zhen Hu
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  3. Xiangyu Liao
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  4. Xing Chen
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  5. Wenrong Huang
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  6. Yu Zhong
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  7. Zhaoyang Zeng
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Corresponding authors

Correspondence to Wufei Zhu or Zhaoyang Zeng.

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Funding

This study was supported by the National Natural Science Foundation of China (grant numbers 81202303 and 31302056), the research plan of the Health Department of Hubei Province (grant number 2012FFB06304), the Science and Technology Plan of Hubei Province (grant number JX6B37), the Health Technology and Development Research Plan of Yichang (grant number A12301-07), and the Research Development Foundation of Center Hospital of Yichang (grant number KFJ2011025).

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhu, W., Hu, Z., Liao, X. et al. A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1. Immunogenetics 69, 643–651 (2017). https://doi.org/10.1007/s00251-017-0995-5

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  • DOI: https://doi.org/10.1007/s00251-017-0995-5

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