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.