X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy

@article{Wildin2001XlinkedND,
  title={X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy},
  author={Robert S. Wildin and Fred Ramsdell and Jane Peake and Francesca Faravelli and Jean Laurent Casanova and Neil R. M. Buist and Ephrat Levy-Lahad and Massimo Mazzella and Olivier Goulet and Lucia Perroni and Franca Dagna Bricarelli and Geoff Byrne and M Mceuen and Sean C. Proll and Mark W. Appleby and Mary E. Brunkow},
  journal={Nature Genetics},
  year={2001},
  volume={27},
  pages={18-20}
}
To determine whether human X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome (IPEX; MIM 304930) is the genetic equivalent of the scurfy (sf) mouse, we sequenced the human ortholog (FOXP3) of the gene mutated in scurfy mice (Foxp3), in IPEX patients. We found four non-polymorphic mutations. Each mutation affects the forkhead/winged-helix domain of the scurfin protein, indicating that the mutations may disrupt critical DNA interactions. 
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TLDR
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Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation.
TLDR
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TLDR
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TLDR
To the Editor: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, a rare disorder characterized by multiorgan autoimmunity, often results in death in infancy, and identification of the functional consequences of individual mutations is critical.
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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.
  Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX)
TLDR
Novel mutations in the FOXP3 gene of two unrelated Japanese patients with X linked autoimmune enteropathy associated with tubulonephropathy and endocrinopathy are reported here.
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TLDR
A clinical case of permanent neonatal diabetes mellitus in the structure of IPEX syndrome is described, which is very important to diagnose it early and start therapy timely.
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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.
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References

SHOWING 1-10 OF 12 REFERENCES
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.
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.
X-linked lymphoreticular disease in the scurfy (sf) mutant mouse.
TLDR
The findings indicate that scurfy disease may be the result of immune dysfunction, but it is not a classic immunodeficiency.
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
X-linked immune dysregulation, neonatal insulin dependent diabetes, and intractable diarrhoea.
TLDR
Four related male infants presented with neonatal diabetes mellitus, immune dysregulation with extremely high concentrations of immunoglobulin E, and intractable diarrhoea and it is suggested that this is a new immunodeficiency in which type 2 T helper responses predominate.
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.
A transcript map of a 2-Mb BAC contig in the proximal portion of the mouse X chromosome and regional mapping of the scurfy mutation.
TLDR
A physical clone contig has been constructed, spanning 2 Mb on the proximal mouse X chromosome containing the mouse scurfy and tattered mutations, and a number of genetic markers have been developed, which has enabled the region containing the sf mutation to be narrowed to <300 kb.
Five years on the wings of fork head
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