Mutations in FOXP3 gene causing<unk>  - known in the year 2012.<unk>  is inherited in males via an x-linked recessive manner, as the FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in this condition's mechanism. The FOXP3 gene has 12 exons and its full reading open frame encodes 431 amino-acids. FOXP3 is a member of the FKH family of transcription factors and contains a proline‐rich (PRR) amino‐terminal domain, central zinc finger (ZF) and leucine zipper (LZ) domains important for protein–protein interactions, and a carboxyl‐terminal FKH domain required for nuclear localization and DNA‐binding activity. In humans, exons 2 and 7 are spliced and excluded from the protein. A large variety of mutations have been found, including single base substitutions, deletions, and splicing mutations. A consequence of malfunctioning FOXP3 expression leads to a defect in Treg production. Those patients do not have circulating CD4+/CD25+/FOXP3+ Treg cells. Reduced expression of FOXP3 has been described, and these patients may express normal levels of dysfunctional protein, which leads to mild symptoms later in life or during the neonatal period. In case of suspicion of<unk>  patients should have genetic testing, even if FOXP31 T cells are present in the periphery. Mutation of FOXP3 leading to expression of malfunctioning protein is often localized in the DNA-binding domain called the forkhead domain. The truncated protein cannot bind to its DNA binding site and thus its function concerning T regulatory lymphocytes development and functioning is impaired. The absence or dysfunction of regulatory T cells is the cause of autoimmune symptoms. Data from 2018 describes over 70 mutations in FOXP3 gene leading to<unk> . Nonetheless, this number is still changing with new cases and discoveries coming. For example in 2010 there were only 20 mutations of FOXP3 known in the literature. FOXP3 pathways FOXP3 can function as both a repressor and a trans‐activator of Treg cells depending on interactions with other proteins. FOXP3 express it's activity by controlling transcription as well as influencing epigenetic changes and posttranscriptional modifications. N‐terminal repressor domain of FOXP3 can change transcription or epigenetic regulation of Treg cells. Transcription activity is changing by interacting of N-terminal domain with Eos, which associates with CtBP1 and forms a corepressor complex that binds the IL2 promoter and enables FOXP3 to repress IL2 transcription in Treg cells. FOXP3 forms complexes with histone deacetylase (HDAC) seven, HDAC9, and the histone acetyl transferase TIP60 converts epigenetic activity of Treg cells. N‐terminal domain of FOXP3 also can to interact with RORγ and RORα antagonizing the action of these transcription factors, thereby inhibiting TH17 cell differentiation. FOXP3 is linked with TCR signaling by downstream transcription factors. All of this findings verify importance of FOXP3 in regulation of transcriptional activity/repression of Treg cells.
IPEX syndrome
EAST syndrome
TAN syndrome
TEMPI syndrome
SUNCT syndrome
VEXAS syndrome
3C syndrome
RIDDLE syndrome