Table 2.
Mutations that target FOXP3 isoform expression ratios cause IPEX.
| cDNA | Protein | Immune dysregulation | Endocrinopathy | Enteropathy | Onset | Case progression | T Cell phenotype [Reference] | |
|---|---|---|---|---|---|---|---|---|
| Exon 2 | c.227del | p.L76Qfs+53 | X | X | X | 5 d | IS | Absence of CD4+CD127lowFOXP3+ cells, CD4+CD127low T cells of carrier express only WT allele (72) |
| Increased Th2 differentiation (73) | ||||||||
| Presence of CD25lowFOXP3low cells, high activation status (74) | ||||||||
| X | X | 1 d | died at 8 mo | N/A (75) | ||||
| c.232_233del | p.M78Gfs*127 | N/A | N/A | N/A | N/A | N/A | FOXP3Δ2 expression upon stimulation (68) | |
| c.239del | p.A80Dfs*49 | N/A | N/A | N/A | N/A | N/A | FOXP3Δ2 expression upon stimulation (68); non-suppressive T cells (76) | |
| c.303_304del | p.F102Hfs*103 | X | X | X | 4 mo | HSCT | N/A (77, 78) | |
| c.305del | p.F102Sfs*27 | X | X | X | 6 mo | IS | High activation status (79), CD4+CD127low T cells of carrier express mostly WT allele | |
| X | 40 y | none | ||||||
| Exon 7 | c.736-2A>C | Aberrant splicing | X | X | X | 2 mo | IS; died at 8 y | Few CD4+FOXP3+ cells, increased Th2/Th17-cell differentiation (80) |
| c.748_750del | p.K250del | X | X | X | 2 mo | IS; HSCT; died at 9 y | N/A (81) | |
| X | X | X | 2 mo | IS | Presence of CD4+CD25+FOXP3low cells (82) | |||
| X | X | 4 mo | IS; HSCT | CD4+CD127low T cells of carrier express WT and mutant allele (72) | ||||
| c.750_752del c.751_753del |
p.E251del p.E251del |
X | X | X | N/A | N/A | N/A (3) | |
| X | X | X | 1 mo | IS; HSCT; died at 4 y | N/A (83) | |||
| c.758T>C | p.L253P | X | X | N/A | HSCT | Absence of CD4+CD25+ cells (84) | ||
| c.767T>C | p.M256T | N/A | N/A | N/A | N/A | N/A | N/A (68) | |
| c.816+2delT | Aberrant splicing | N/A | N/A | N/A | 6 mo | HSCT | N/A (69) | |
| c.816+2T>A | Aberrant splicing | X | X | X | N/A | HSCT | Absence of CD25+CD127low cells, FOXP3Δ7 and FOXP3Δ2Δ7 expression upon stimulation (67) | |
| c.816+3G>C | Aberrant splicing | N/A | N/A | N/A | N/A | N/A | N/A (68) | |
| c.816+4A>G | Aberrant splicing | X | X | 2 mo | Died at 3 y | N/A (85) | ||
| X | X | X | 1 d | IS | Increased Th17-cell differentiation (together with other mutations) (86) | |||
| c.816+5G>A | Aberrant splicing | X | X | 6 mo | IS; died at 9 y | FOXP3 expression in CD25− T cells (83) | ||
| X | X | 2 mo | IS; HSCT | |||||
| X | X | X | 1 d | IS; HSCT | ||||
| X | X | N/A | HSCT | Low FOXP3 expression (84) | ||||
| X | X | X | N/A | IS; died at 9 mo | N/A (87) | |||
| c.816+7G>C | Aberrant splicing | X | X | d-mo (6 boys) | Death before 5 y | N/A (85) | ||
| X | X | X | N/A | N/A | N/A (88) |
X, symptoms mentioned in case report; N/A, data not available; IS, immunosuppressive drug treatment; HSCT, hematopoietic stem cell transplantation; d, days; mo, months; y, years.