title: Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome.
abstract: OBJECTIVE
  Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare systemic autoimmune disorder of monogenic and autosomal-recessive inheritance. To date, 29 APECED causing mutations have been identified in the responsible gene AIRE-1, coding for a regulator of transcription. The aim of this study was to examine whether mutations in AIRE-1, in their heterozygous form, predispose to the more common isolated autoimmune endocrinopathies Addison's disease, type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis.
  
  
  METHODS
  Patients with isolated autoimmune endocrine disorders as well as healthy controls were analysed for two of the most common AIRE-1 mutations, mutation R257X in exon 6 and a 13-bp deletion in exon 8. Mutations were detected by polymerase chain reaction based techniques.
  
  
  METHODS
  In total, 726 individuals were investigated for mutation R257X. Subjects comprised patients with Addison's disease, IDDM, Graves' disease and Hashimoto's thyroiditis. With regard to the 13 bp deletion we could screen 91 patients with Addison's disease. In addition, six patients with the APECED syndrome including one family were analysed for both mutations.
  
  
  RESULTS
  Out of the 12 alleles in APECED patients six contained either mutation R257X or the 13 bp deletion, confirming that these mutations prevail in Europe. R257X was found in one subject with Hashimoto's thyroiditis in its heterozygous form. The 13 bp deletion was not detected in any subject with Addison's disease.
  
  
  CONCLUSIONS
  The two studied AIRE-1 mutations are so rare in the general population that they can not contribute to susceptibility for the more common isolated autoimmune disorders.
authors: Medical Department I, Division of Endocrinology, Centre of Internal Medicine, Johann Wolfgang Goethe-University Hospital, Frankfurt-am-Main, Germany.
authors: G
authors: G
authors: Meyer
authors: H
authors: H
authors: Donner
authors: J
authors: J
authors: Herwig
authors: H
authors: H
authors: Böhles
authors: K H
authors: KH
authors: Usadel
authors: K
authors: K
authors: Badenhoop
mesh_terms: D000224:Addison Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein