Clinical and immunological characteristics of five patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in China-expanding the atypical phenotypes

Front Immunol. 2022 Aug 24;13:972746. doi: 10.3389/fimmu.2022.972746. eCollection 2022.


Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulatory system caused by forkhead box P3 (FOXP3) mutations. Abnormal numbers or functions of regulatory T (Treg) cells account for the various autoimmune symptoms. We aimed to explore the molecular genetics and phenotypic spectra of patients with atypical IPEX syndrome in China.

Methods: We analyzed the molecular, clinical and immune phenotype characteristics of five Chinese patients with FOXP3 mutations.

Results: We summarized the molecular and phenotypic features of five patients with FOXP3 mutations, including two novel mutations. Four of the five patients displayed atypical phenotypes, and one developed immune-related peripheral neuropathy. Three of the five patients showed normal frequencies of Treg cells, but the proportions of subsets of Treg cells, CD4+ T cells and B cells were out of balance.

Conclusions: Our report broadens the understanding of the clinical features of atypical IPEX syndrome. Our detailed analyses of the immunological characteristics of these patients enhance the understanding of the possible mechanisms underlying the clinical manifestations.

Keywords: FOXP3 mutations; IPEX syndrome; atypical phenotypes; primary immunodeficiency disease; regulatory T cells.

MeSH terms

  • Diabetes Mellitus, Type 1 / congenital
  • Diabetes Mellitus, Type 1 / genetics
  • Diarrhea / etiology
  • Diarrhea / genetics
  • Forkhead Transcription Factors* / genetics
  • Genetic Diseases, X-Linked / genetics
  • Humans
  • Immune System Diseases / congenital
  • Immune System Diseases / genetics
  • Intestinal Diseases / congenital
  • Intestinal Diseases / genetics
  • Phenotype
  • Polyendocrinopathies, Autoimmune* / congenital
  • Polyendocrinopathies, Autoimmune* / genetics
  • Syndrome


  • FOXP3 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome