title: Autoimmune polyglandular syndrome type 1 in Russian patients: clinical variants and autoimmune regulator mutations.
abstract: BACKGROUND
  Autoimmune polyglandular syndrome type 1 (APS-1) (OMIM 240300) is a rare autosomal recessive disorder associated with three major manifestations: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. There are, however, multiple minor components of APS-1 that induce significant phenotype variability. Subsequently, the diagnosis of APS-1 during early stages is often challenging.
  
  
  OBJECTIVE
  We aimed to provide clinical and mutational data for a large number of APS-1 patients in the Russian population.
  
  
  METHODS
  We analyzed clinical variations and component prevalence in APS-1 patients. DNA screening for autoimmune regulator (AIRE) gene mutations was performed in established APS-1 patients and in patients with the single components of chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, or alopecia.
  
  
  RESULTS
  We identified 46 patients from 42 families with APS-1. Eighteen different components were present in the patients, including very rare conditions - bone dysplasia and retinitis pigmentosa. We identified 10 different mutations, 3 of which were novel (M1T, E298K, c1053_1060del). The common Finnish mutation, R257X, was the most frequent in our population, present in 64/92 (70%) of the alleles.
  
  
  CONCLUSIONS
  We found that the R257X AIRE mutation is common in Russian APS-1 patients. The majority of children with hypoparathyroidism and chronic mucocutaneous candidiasis were carriers of the AIRE mutations.
authors.affiliation: Endocrinology Research Centre, Institute of Paediatric Endocrinology, Moscow, Russia. elizaveta.orlova @ mail.ru
authors.forename: Elizaveta M
authors.initials: EM
authors.lastname: Orlova
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bukina
authors.forename: Elvira S
authors.initials: ES
authors.lastname: Kuznetsova
authors.forename: Maria A
authors.initials: MA
authors.lastname: Kareva
authors.forename: Ekaterina U
authors.initials: EU
authors.lastname: Zakharova
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Peterkova
authors.forename: Ivan I
authors.initials: II
authors.lastname: Dedov
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D012426:Russia
chemical_list: D001323:Autoantibodies