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

作者：Jin, Ping; Zhang, Qin; Dong, Chang-sheng; Zhao, Shao-li; Mo, Zhao-Hui^*

来源：JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2014, 37(10): 941-948.

DOI：10.1007/s40618-014-0120-7

• Autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy syndrome
• Autoimmune regulator gene
• Autoimmune polyendocrine syndrome type 1
• Mutation

Introduction 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.
The purpose of this study was to identify the underlying genetic cause in a Chinese family diagnosed with APECED.
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.
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.
We identified a novel AIRE mutation which alters the intracellular location and transcription activity of AIRE, and has implications in the pathogenesis of APECED.

• 出版日期2014-10
• 单位中南大学