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A novel mutation in autoimmune regulator gene causes autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

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Abstract

Background

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive disease due to mutations in the autoimmune regulator (AIRE) gene, which encodes a transcription factor that induces the expression of peripheral tissue-specific antigens in medullary thymic epithelial cells.

Aim

The purpose of this study was to identify the underlying genetic cause in a Chinese family diagnosed with APECED.

Method

Peripheral blood samples were collected from family members. All exons of the AIRE gene and adjacent exon–intron sequences were amplified by PCR and subsequently sequenced. The functional consequence of the mutations was analyzed by cell transfection and in vitro assays.

Results

A novel c.483_484insC mutation in exon 4 was identified, which resulted in a frame shift predicted to generate a truncated protein containing the first 163 AIRE amino acids followed by 52 aberrant amino acids. Confocal immunofluorescence microscopy of COS-7 cells transfected with wild-type and mutant AIRE constructs showed that wild-type AIRE protein was localized mainly in the nucleus, while mutant AIRE was localized mainly in the cytoplasm. A luciferase reporter assay showed that the identified mutation dramatically inhibited the transactivation activity of AIRE in vitro.

Conclusion

We identified a novel AIRE mutation which alters the intracellular location and transcription activity of AIRE, and has implications in the pathogenesis of APECED.

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Acknowledgments

We are grateful to all family members included in this study for their invaluable participation and cooperation. This study was supported by the National Science Foundation for Young Scholars of China (81100583), Natural Science Foundation of China Hunan Province (12JJ4083), Social Development Supporting Plan Program of Science and Technology Bureau of Hunan Province (2011SK3242), and the Freedom to Explore Program of Central South University (2011QNZT191).

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Endorcrinology, 3nd Xiangya Hospital, Central South University, Tongzipo Road, Changsha, 410007, Hunan, People’s Republic of China

    Ping Jin, Qin Zhang, Shao-li Zhao & Zhao-Hui Mo

  2. Department of Anesthesia, The Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410007, Hunan, People’s Republic of China

    Chang-sheng Dong

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  1. Ping Jin
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  2. Qin Zhang
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Correspondence to Zhao-Hui Mo.

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Jin, P., Zhang, Q., Dong, Cs. et al. A novel mutation in autoimmune regulator gene causes autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Endocrinol Invest 37, 941–948 (2014). https://doi.org/10.1007/s40618-014-0120-7

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  • DOI: https://doi.org/10.1007/s40618-014-0120-7

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