title: Autoimmune polyendocrine syndrome type 1 in north-western France: AIRE gene mutation specificities and severe forms needing immunosuppressive therapies.
abstract: BACKGROUND
  Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations.
  
  
  METHODS
  Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing.
  
  
  RESULTS
  Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1-10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected.
  
  
  CONCLUSIONS
  APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.
authors.forename: E
authors.initials: E
authors.lastname: Proust-Lemoine
authors.forename: P
authors.initials: P
authors.lastname: Saugier-Véber
authors.forename: D
authors.initials: D
authors.lastname: Lefranc
authors.forename: S
authors.initials: S
authors.lastname: Dubucquoi
authors.forename: A
authors.initials: A
authors.lastname: Ryndak
authors.forename: D
authors.initials: D
authors.lastname: Buob
authors.forename: J D
authors.initials: JD
authors.lastname: Lalau
authors.forename: R
authors.initials: R
authors.lastname: Desailloud
authors.forename: J
authors.initials: J
authors.lastname: Weill
authors.forename: L
authors.initials: L
authors.lastname: Prin
authors.forename: H
authors.initials: H
authors.lastname: Lefebvre
authors.forename: J L
authors.initials: JL
authors.lastname: Wémeau
mesh_terms: D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000453:epidemiology / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005602:France / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D007166:Immunosuppressive Agents; D014157:Transcription Factors; D000096927:AIRE Protein