title: Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) and in their relatives.
abstract: OBJECTIVE
  Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare syndrome characterized by chronic candidiasis, chronic hypoparathyroidism and Addison's disease. APECED has been associated with mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic analysis of the AIRE gene in Italian APECED patients and in their relatives. Design AIRE mutations were determined by DNA sequencing in all subjects. Patients were tested for clinical autoimmune or non-autoimmune diseases, or for organ and non-organ specific autoantibodies.
  
  
  METHODS
  A total of 24 Italian patients with APECED (15 from the Venetian region, 2 from Southern-Tyrol, 4 from Apulia, 3 from Sicily), 25 relatives and 116 controls were studied.
  
  
  RESULTS
  Ten out of the 15 Venetian patients (66%) were homozygous for R257X or compound heterozygous with 1094-1106del13. One patient was homozygous for 1094-1106del13 and another for R139X. A novel mutation (1032-1033delGT) in combination with 1094-1106del13 was identified in one patient. No mutations were found in two cases. Two patients from Southern Tyrol were homozygous for R257X and for 1094-1106del13bp. All patients from Apulia were homozygous or heterozygous for W78R combined with Q358X. The patients from Sicily were homozygous for R203X or compound heterozygous with R257X. The analysis of the genotype-phenotype revealed that patients carrying 1094-1106del13 at the onset of Addison's disease were significantly older than those carrying other mutations. The genetic study of 25 relatives identified 20 heterozygous subjects. They suffered from various autoimmune and non-autoimmune diseases but no major disease of APECED was found.
  
  
  CONCLUSIONS
  These data demonstrate the great genetic heterogeneity for the AIRE mutations in Italian APECED patients, and that the heterozygosity for AIRE mutations do not produce APECED.
authors.affiliation: Division of Endocrinology, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cervato
authors.forename: Barbara
authors.initials: B
authors.lastname: Mariniello
authors.forename: Francesca
authors.initials: F
authors.lastname: Lazzarotto
authors.forename: Luca
authors.initials: L
authors.lastname: Morlin
authors.forename: Renato
authors.initials: R
authors.lastname: Zanchetta
authors.forename: Giorgio
authors.initials: G
authors.lastname: Radetti
authors.forename: Filippo
authors.initials: F
authors.lastname: De Luca
authors.forename: Mariella
authors.initials: M
authors.lastname: Valenzise
authors.forename: Roberta
authors.initials: R
authors.lastname: Giordano
authors.forename: Daniela
authors.initials: D
authors.lastname: Rizzo
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
mesh_terms: D000224:Addison Disease / Q000208:ethnology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D002177:Candidiasis / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007011:Hypoparathyroidism / Q000208:ethnology / Q000235:genetics; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016884:Polyendocrinopathies, Autoimmune / Q000208:ethnology* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein