A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1
- 24 May 2017
- journal article
- case report
- Published by Springer Science and Business Media LLC in Immunogenetics
- Vol. 69 (10), 643-651
- https://doi.org/10.1007/s00251-017-0995-5
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.Keywords
Funding Information
- The National Natural Science Foundation of China (31302056, 81202303)
- The Health Department of Hubei Province (2012FFB06304)
- The Science and Technology Plan of Hubei Province (JX6B37)
- The Health Technology and Development Research Plan of Yichang (A12301-07)
- The Research Development Foundation of Center Hospital of Yichang (KFJ2011025)
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