Table 1.
Genetics and main phenotypical features of 14 patients with STAT1 GOF mutations.
| Mutation (cDNA)/(amino acid) | Affected domain | Sex | Age (y) | Clinical onset | CMC | Infections | Autoimmunity/inflammatory | Endocrinopathy | Immunosuppressive therapy at the time of the study | |
|---|---|---|---|---|---|---|---|---|---|---|
| P1 | c.(493G>C) D165H (2) |
CCD | M | 30 | 1st year of life | Oral cavity, esophagus, skin and genital mucosa | Recurrent sinopulmonary infections; HSV esophagitis; recurrent herpes zoster | Upper GI ulcers | Type 1 DM | None |
| P2 | c.(704A>G) E235G (9) |
CCD | F | 62 | 1st year of life | Oral cavity, skin and genital mucosa | Recurrent sinopulmonary infections; bacterial skin infections with abscesses; recurrent HSV labialis | Alopecia | None | |
| P3 | c.(704A>G) E235G (9) |
CCD | F | 34 | 1st week of life | Oral cavity | Recurrent sinopulmonary infections | None | ||
| P4 | c.(800 C>T) A267V (1, 3) |
CCD | M | 19 | 6 months old | Oral cavity, esophagus and skin | Recurrent RSV; Mycobacterium fortuitum lymphadenitis | None | ||
| P5 | c.(820C>T) R274W (1, 10) |
CCD | F | 30 | 1st year of life | Oral cavity, esophagus and genital mucosa | Recurrent pneumonia; recurrent bacteremia; bacterial skin infections | Myopathy; SLE | Type I DM | Ruxolitinib |
| P6 | c.(821G>A) R274Q (1, 2, 10) |
CCD | F | 30 | 3 years old | Oral cavity, esophagus, skin and genital mucosa | Recurrent sinopulmonary infections; bacterial skin infections with abscesses; recurrent herpes zoster | None | ||
| P7 | c.(821G>A) R274Q (1, 2, 10) |
CCD | M | 4 | 3 years old | Oral cavity and genital mucosa | None | |||
| P8 | c.(963A>T) R321S (11, 12) |
DBD | F | 18 | 6 years old | Skin | Recurrent sinopulmonary infections; bacterial skin infections; dermatophytosis; recurrent herpes zoster | Alopecia | Hypothyroidism; GH deficiency | None |
| P9 | c.(963A>T) R321S (11, 12) |
DBD | F | 21 | 6 years old | Oral cavity and skin | Recurrent sinopulmonary infections; bacterial skin infections with abscesses; dermatophytosis; warts | Autoimmune hepatitis; alopecia | Type I DM | None |
| P10 | c.(963A>T) R321S (11, 12) |
DBD | M | 25 | 1st year of life | Oral cavity, esophagus and skin | Recurrent sinopulmonary infections; disseminated MAC; severe acute varicella zoster infection; Parvo B19 viremia; BK viruria; HCV | Cytopenia; HLH | GH deficiency | None |
| P11 | c.(983A>G) H328R |
DBD | M | 10 | 1st year of life | Recurrent sinopulmonary infections | Colitis | Hypothyroidism; Type I DM; GH deficiency | HSCT with low chimerism 5 years prior to the study | |
| P12 | c.(1057G>A) E353K (3) |
DBD | M | 27 | 14 years old | Disseminated coccidioidomycosis; dermatophytosis | Ruxolitinib | |||
| P13 | c.(1154C>T) T385M (3, 4, 10) |
DBD | M | 27 | 1st week of life | Oral cavity and skin | Histoplasma pneumonia; recurrent herpes zoster; Mycobacterium fortuitum lymphadenitis | None | ||
| P14 | c.1885C>T H629Y (13) |
SH2D | F | 25 | 1st year of life | Oral cavity and genital mucosa | Recurrent pneumonia requiring lobectomy; rectal abscesses; C. dif; recurrent herpes zoster | Rectovaginal fistula | Hypothyroidism | None |
CCD, coiled-coil domain; CMC, chronic mucocutaneous candidiasis; C. diff., Clostridium difficile; DBD, DNA-binding domain; DM, Diabetes mellitus; GH, growth hormone; HSCT, Hematopoietic stem cell transplantation; HCV, Hepatitis C virus; HSV, Herpes simplex virus; MAC, Mycobacterium avium complex; RSV- respiratory syncytial virus.
References for the nine mutations that were published in the past are in parentheses.