Patient | Mutation | Clinical features | Histology | Management | Outcome | Ref. | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Age at onset age at dg | Nucleotide change | AA change | FOXP3 | Molecular defect | Previous therapy | SIR | HSCT | |||||
1 | 7 y 10 y | c.968-20A>C | NA | NA | NA | Dermatitis, enteropathy | Lymphoplasmocellular eosinophilic infiltrate. Villous atrophy. | Steroids, AZA, CsA, FK, MTX. TPN, Total colectomy at 10 y | Y | N | Stable at 16 yr on SIR+MTX. | [19] |
2* | 2 m NA | NA | Enteropathy, erythematous eczema-like dermatitis | Lymphoplasmocellular infiltrate with marked eosinophilia. High rate of enterocyte apoptosis. Subtotal villous atrophy. | Steroids, FK, AZA | Y | N | Stable for 1.5 yr on SIR+AZA | [19] | |||
3* | 2 m NA | NA | Enteropathy, erythematous eczema-like dermatitis | Similar findings with that of his brother (pt.4) | Steroids, FK; AZA | Y | N | Stable for 6 m on SIR+AZA | [19] | |||
4 | 2 y 4 y | 1061 delC | Frameshift P354Q | NA | Premature stop codon. Truncated FKH domain | Enteropathy, nonspecific dermatitis | Mild villous blunting | Metronidazole, steroids, mesalamine, IFX, AZA, 6-MP | Y | N | Stable at 7 yr | [20] |
5 | 1 w 7 y | 200G>T | Q70H | NA | Predicted abnormal reading frame | Eczema, enteropathy, AHA, ITP, arthritis | Inflammation with villous atrophy | IVIG, steroids, TPN, antibiotics | Y | N | Stable at 8 yr | |
6* | 3 w NA | g.-6247-4859del | NA | ↓ | Accumulation of unspliced mRNA | Skin/food allergies, Enteropathy, erythematous- eczematous skin rash | Lymphoplasmocellular infiltrate with marked eosinophilia. High rate of enterocytes apoptosis. Severe to total villous atrophy | Steroids, FK, AZA TPN | Y | N | Stable for 6 yr on SIR+AZA | [22] |
7* | 2 m NA | g.-6247-4859del | NA | ↓ | Accumulation of unspliced mRNA | Skin/food allergies, Eczema, Enteropathy | NA | Steroids, FK, AZA TPN | Y | N | Stable for 4 yr on SIR+AZA | [22] |
8 | 5 w NA | g.-6247-4859del | NA | ↓ | Accumulation of unspliced mRNA | Enteropathy, Eczema, Allergy | NA | Steroids, FK, AZA | Y | N | Stable at 9 yr on SIR+AZA | [23] |
9 | 3 w NA | g.-6247-4859del | NA | ↓ | Accumulation of unspliced mRNA | Enteropathy, Eczema, HP gastritis, Allergy | NA | Steroids, FK AZA | Y | N | Stable at 6 yr on SIR+AZA | [23] |
10 | Birth NA | g.-1121 T>G | F374C | ↓ | Full length FOXP3 with abnormal FKH domain | T1DM, HTH, Enteropathy, Eczema, AHA, ITP, Allergy. | NA | Steroids, FK506 | Y | N | Died at 14 m during HSCT induction | [23] |
11 | 6 w NA | 751-753 del GAG | E251del | ↓ | Disrupts FOXP3 oligomerisation | Enteropathy, Eczema, HTH, Interstitial Nephritis, AHA, Allergy. | NA | FK506 | Y | Y | Died at 10 yr after HSCT | [23] |
12 | 1 m 6 y | 1150G>A | A384T | ↓ | Full length FOXP3 with abnormal FKH domain | Enteropathy, Eczema, FTT, T1DM, AHA, Interstitial Pneumonia, Alopecia, Thyroiditis. | Eosinophil infiltration without villous atrophy | IVIG, CsA, steroids, TPN, fludarabine-autologous lymphocytes, FK, MTX, Rituximab, cyclophosphamide. | Y | N | Stable at 16 yr on others drugs | |
13 | Birth 7 w | 1150G>A | A384T | ↓ | Full length FOXP3 with abnormal FKH domain | Enteropathy, T1DM, Exfoliative Dermatitis, HTH, Pancytopenia | NA | TPN | Y | N | Died at 7 w | [26] |
14 | Birth 4½ y | AAUAAA/AAUAAG | NA | ↓ | Polyadenylation defect resulting in unstable FOXP3 mRNA | Enteropathy, Dermatitis, FTT, T1D. | NA | MTX, steroids, TPN. | Y | Y | Stable at 1 yr | [27] |
15 | 1 w | 1015C>G | P339A | ↓ | Missense mutation. Predicted to yield full length FOXP3 | Enteropathy, Eczema, T1DM, FTT, Euthyroid Thyroiditis, AIH, AHA | Villous atrophy | Steroids, FK; AZA | Y | N | Died at 5.5 m before HSCT | [28] |
16 | 3 m 1y | Exon 10 | NA | NA | NA | FTT, Enteropathy, Eczematous Dermatitis, ITP stomatitis | NA | Cyclophosphamide, VCR, TPN | Y | N | Stable 2½ yr on other drugs | [29] |