The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3

@article{Bennett2001TheID,
  title={The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3},
  author={Craig L. Bennett and Jacinda R. Christie and Fred Ramsdell and Mary E. Brunkow and Polly J. Ferguson and Luke Whitesell and Thaddeus E. Kelly and Frank T. Saulsbury and Phillip F. Chance and Hans D. Ochs},
  journal={Nature Genetics},
  year={2001},
  volume={27},
  pages={20-21}
}
IPEX is a fatal disorder characterized by immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance (MIM 304930). We present genetic evidence that different mutations of the human gene FOXP3, the ortholog of the gene mutated in scurfy mice (Foxp3), causes IPEX syndrome. Recent linkage analysis studies mapped the gene mutated in IPEX to an interval of 17–20-cM at Xp11.23–Xq13.3 (refs. 1,2). 

Figures and Tables from this paper

Cutaneous manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome
TLDR
This data indicates that IPEX syndrome is a rare disorder characterized by neonatal autoimmune enteropathy, diabetes and thyroiditis, food allergies and skin rash caused by mutations in FOXP3, a master control gene of regulatory T cells (Tregs), resulting in absent or dysfunctional Tregs.
The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome
TLDR
The genetic, immunological and clinical characteristics of IPEX syndrome are described, and the impact of heritable mutations on the function of Treg cells highlighted.
IPEX as a Result of Mutations in FOXP3
TLDR
Apart from its clinical implications, IPEX illustrates the importance of immunoregulatory cells such as CD4+CD25+ regulatory T cells such in immune homeostasis and protection against autoimmunity.
Late-onset of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome (IPEX) with intractable diarrhea
TLDR
The case of a twelve-year old male affected by a very late-onset IPEX with intractable enteropathy, which markedly improved after starting Sirolimus as second-line treatment, suggests that IPEX should always be considered in the differential diagnosis of watery intractables diarrhea, despite its unusual onset.
A Mystery Diagnosis: Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Recessive
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), a rare disease, has recently been shown to occur more frequently than previously suspected. The clinical phenotype of
Renal Involvement in IPEX Syndrome With a Novel Mutation of FOXP3: A Case Report
TLDR
A rare case of IPEX syndrome caused by a novel variant of FOXP3, with clinical manifestations including autoimmune hemolysis, bronchiectasis, diarrhea, and proteinuria but without diabetes or other endocrine disorders is presented.
Intractable Diarrhea and Failure to Thrive
TLDR
Treg cells enumeration and Foxp3 protein expression are used as screening tests for IPEX syndrome; however, confirmation of pathogenic variants by sequencing the FOXP3 gene is required.
The immunological and genetic basis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome
TLDR
An in-depth structural and functional analysis of the molecular domains of FOXP3 is essential for the understanding of the observed clinical heterogeneity and prognosis in IPEX.
Persistent Enteropathy in a Toddler with a Novel FOXP3 Mutation and Normal FOXP3 Protein Expression.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 12 REFERENCES
X-Linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea maps to Xp11.23-Xq13.3.
We describe genetic analysis of a large pedigree with an X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea (XPID), which frequently results in death during infancy or
Manifestations and linkage analysis in X-linked autoimmunity-immunodeficiency syndrome.
TLDR
It is concluded that this kindred has an X-linked disorder, distinct from WAS, that results in autoimmunity and variable immunodeficiency, which includes the Wiskott-Aldrich syndrome locus.
The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.
The X chromosome-linked scurfy (sf) mutant of the mouse is recognized by the scaliness of the skin from which the name is derived and results in death of affected males at about 3-4 weeks of age.
Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25
TLDR
A three-generation family with Axenfeld-Rieger syndrome, harboring an alteration in the forkhead-like 7 (FKHL7) gene, broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.
Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse
TLDR
Genetic complementation demonstrates that the protein product of Foxp3, scurfin, is essential for normal immune homeostasis.
Cellular and molecular characterization of the scurfy mouse mutant.
TLDR
Flow cytometric analyses of lymphoid cell populations reveal that scurfy syndrome is characterized by changes in several phenotypic parameters, including an increase in Mac-1+ cells and a decrease in B220+ cells, changes that may result from the production of extremely high levels of the cytokine granulocyte-macrophage CSF by scurfi T cells.
Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia
TLDR
The transcription factor FKHL15 (ref. 11) is the human homologue of mouse TTF-2 (encoded by the Titf2 gene) and that two siblings with thyroid agenesis, cleft palate and choanal atresia are homozygous for a missense mutation (Ala65Val) within its forkhead domain.
The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25
TLDR
FKHL7, encoding a forkhead transcription factor, is in close proximity to the breakpoint in the balanced translocation patient and is deleted in a second PCG patient with partial 6p monosomy, demonstrating that mutations in FKHL 7 cause a spectrum of glaucoma phenotypes.
Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly.
TLDR
These findings demonstrate that, although mutations of FKHL7 result in anterior-segment defects and glaucoma in some patients, it is probable that at least one more locus involved in the regulation of eye development is also located at 6p25.
...
1
2
...