title: A novel mutation in autoimmune regulator gene causes autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
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.
  
  
  OBJECTIVE
  The purpose of this study was to identify the underlying genetic cause in a Chinese family diagnosed with APECED.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  We identified a novel AIRE mutation which alters the intracellular location and transcription activity of AIRE, and has implications in the pathogenesis of APECED.
authors: Department of Endorcrinology, 3nd Xiangya Hospital, Central South University, Tongzipo Road, Changsha, 410007, Hunan, People's Republic of China.
authors: Ping
authors: P
authors: Jin
authors: Qin
authors: Q
authors: Zhang
authors: Chang-Sheng
authors: CS
authors: Dong
authors: Shao-Li
authors: SL
authors: Zhao
authors: Zhao-Hui
authors: ZH
authors: Mo
mesh_terms: D000328:Adult; D002681:China; D003241:Consanguinity; D005260:Female; D006801:Humans; D009154:Mutation; D010375:Pedigree; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein