Autoimmune polyglandular syndrome type 1 in Russian patients: clinical variants and autoimmune regulator mutations

Horm Res Paediatr. 2010;73(6):449-57. doi: 10.1159/000313585. Epub 2010 Apr 20.

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.

Aim: 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / immunology
  • Autoimmunity / immunology
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Polyendocrinopathies, Autoimmune / diagnosis
  • Polyendocrinopathies, Autoimmune / genetics*
  • Polyendocrinopathies, Autoimmune / immunology*
  • Russia

Substances

  • Autoantibodies