Two novel mutations of the AIRE protein affecting its homodimerization properties

Hum Mutat. 2005 Mar;25(3):319. doi: 10.1002/humu.9309.

Abstract

We report two novel mutations, c.230T>C (p.F77S) and c.64_69del (p.V22_D23del) within the HSR domain of the AIRE protein in two patients of Italian descent affected by APECED. Both mutations were found in the compound heterozygous state respectively with c.994+5G>T and c.232T>A (p.W78R). With the two-hybrid assay in the yeast system we found that constructs containing the two mutations fail to interact with the wild-type protein. These findings indicate that both mutations negatively affected the homodimerization properties of the AIRE protein, thereby leading to a defective function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIRE Protein
  • Adult
  • Amino Acid Sequence
  • Child
  • Dimerization
  • Female
  • Heterozygote
  • Humans
  • Italy
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation, Missense*
  • Point Mutation*
  • Polyendocrinopathies, Autoimmune / genetics*
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Sequence Deletion*
  • Sequence Homology, Amino Acid
  • Sicily
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Two-Hybrid System Techniques

Substances

  • Transcription Factors