Rapid whole-genome sequencing identifies a novel AIRE variant associated with autoimmune polyendocrine syndrome type 1

Cold Spring Harb Mol Case Stud. 2018 Jun 1;4(3):a002485. doi: 10.1101/mcs.a002485. Print 2018 Jun.


Autoimmune polyendocrine syndrome type 1 (APS-1; OMIM #240300), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. APS-1 is classically characterized by a triad of chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and autoimmune adrenocortical insufficiency. We report a 5-yr-old female who presented with symptoms of tetany due to hypocalcemia and was subsequently found to be secondary to hypoparathyroidism. Rapid trio whole-genome sequencing revealed compound heterozygous variants in AIRE in the proband, with a paternally inherited, pathogenic, frameshift variant (c.1265delC; p.Pro422LeufsTer58) and a novel, likely pathogenic, maternally inherited missense variant (c.268T>C; p.Tyr90His).

Keywords: autoimmune hypoparathyroidism; hyperphosphatemia; hypocalcemic seizures.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Child, Preschool
  • Chromosome Mapping
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Mutation*
  • Phenotype*
  • Polyendocrinopathies, Autoimmune / diagnosis*
  • Polyendocrinopathies, Autoimmune / genetics*
  • Transcription Factors / genetics*
  • Whole Genome Sequencing*


  • APECED protein
  • Transcription Factors