Table 1.
Mode of inheritance and molecular studies in the 170 Tunisian patients investigated.
| PID | Gene | Mode of inheritance | Number of kindred | Number of patients | Confirmed parental consanguinity | Molecular defects |
Recurrent mutation | Novel mutation | |
|---|---|---|---|---|---|---|---|---|---|
| cDNA | Protein | ||||||||
| Immunodeficiencies affecting cellular and humoral immunity (n = 53) | |||||||||
| SCID | IL2RG | XL | 1 | 2 | – | c.865C>T | R289X | – | – |
| 1 | 3 | – | c.710G>A | W237X | – | + | |||
| 1 | 2 | – | c.222G>A | W74X | – | + | |||
| RAG 2 | AR | 1 | 1 | 1 | c.1219G>T | E407X | – | – | |
| 2 | 2 | 2 | c.1338C>G | C446W | – | – | |||
| IL7RA | AR | 1 | 1 | 1 | c.616 C>T | R206X | – | – | |
| PNP | AR | 1 | 1 | 1 | c.181 + 1G>A | – | – | + | |
| Omenn syndrome | RAG1 | AR | 7 | 9 | 8 | 631delT | T173TfsX28 | + | – |
| MHC-II deficiency | RFXANK | AR | 23 | 27 | 19 | c.338-25_338del26 | I5E6-25_I5E6 + 1 | + | – |
| HIGE—DOCK8 deficiency | DOCK8 | AR | 1 | 1 | 1 | Ex1-43 del | – | – | + |
| HIGM—CD40 ligand deficiency | CD40LG | XL | 1 | 1 | – | c.348_351dup | Q118Vfs*5 | – | + |
| 1 | 1 | – | c.782_*2del | L261Qfs*50 | – | + | |||
| 1 | 1 | – | c.[356G>A; 299_356del] | p.([116G>S, D97_K115del]) | – | – | |||
| HIGM—CD40 deficiency | CD40 | AR | 1 | 1 | 1 | c.109T>G | C37G | – | + |
| Combined immunodeficiencies with associated or syndromic features (n = 19) | |||||||||
| HIES | STAT 3 | AD | 1 | 4 | – | c.1298A>G | M329V | – | + |
| 1 | 1 | – | c.1858A>G | T620A | – | – | |||
| PGM3 | AR | 3 | 12 | 10 | c.1018_1020del | E340del | + | + | |
| 1 | 2 | 2 | c.248T>C | L83S | – | + | |||
| Predominantly antibody deficiencies (n = 26) | |||||||||
| XLA | BTK | XL | 2 | 2 | – | c.1762T>G | W588G | – | + |
| 1 | 1 | 1 | c.863G>A | R288Q | – | – | |||
| 2 | 2 | 1 | c.435C>A | C145X | – | – | |||
| 1 | 1 | – | c.1117C>T | L373V | – | + | |||
| 1 | 1 | – | c.1567 − 1G>A | – | – | + | |||
| 1 | 1 | 1 | c.1181C>G | S394X | – | + | |||
| 1 | 2 | 2 | c.1631 + 1G>A | – | – | – | |||
| 1 | 1 | 1 | c.653delA | K218fsX228 | – | – | |||
| 1 | 1 | – | c.1845_1846insGT | L616fsX649 | – | + | |||
| IGHM | AR | 1 | 1 | 1 | c.1789insCC1792-1796del CCAGC | V378AfsX1 | – | + | |
| TCF3 | AR | 1 | 2 | 2 | c.808C>T | Q270X | – | + | |
| HIGM—AID deficiency | AICDA | AR | 1 | 1 | – | c.91T>C | Y31H | – | + |
| 4 | 5 | 4 | c.389A>C | H130P | + | + | |||
| 3 | 5 | 3 | c.156 + 1G>T | ([N53Lfs*15, N53Lfs*19]) | + | –a | |||
| Diseases of immune dysregulation (n = 10) | |||||||||
| ALPS | FAS | AD | 1 | 1 | – | c.266G>A | A16T | – | – |
| 1 | 1 | – | c.926G>A | E194K | – | – | |||
| 1 | 1 | – | c.365C>T | T122I | – | – | |||
| 1 | 1 | – | c.1009A>G | E256G | – | – | |||
| AR | 1 | 4 | 3 | c.1017A>G | N266S | – | + | ||
| 1 | 2 | 1 | c.581C>T | R121W | – | + | |||
| Congenital defects of phagocyte number, function, or both (n = 37) | |||||||||
| CGD | NCF2 | AR | 6 | 11 | 9 | c.257 + 2T>C | A59IfsX2 | + | –a |
| 1 | 1 | 1 | c.78A>T | N419I | – | + | |||
| NCF1 | AR | 5 | 5 | 2 | c.75_76delGT | – | – | – | |
| CYBA | AR | 1 | 1 | – | 295-301delGTGCCCG | – | – | + | |
| 1 | 1 | – | c.70G>A | G24R | – | – | |||
| CYBB | XL | 1 | 1 | – | c.1359G>A | W453X | – | + | |
| LAD I | CD18 | AR | 10 | 15 | 11 | c.119_128delGGCCCGGCTG | G40A fsX7 | + | – |
| 2 | 2 | 2 | c.1777C>T | R593C | – | – | |||
| Defects in intrinsic and innate immunity (n = 23) | |||||||||
| MSMD | IL12B | AR | 7 | 9 | 4 | c.298_305del | – | + | + |
| IL12RB1 | AR | 1 | 1 | – | 622C>A | C185X | – | + | |
| 1 | 1 | 1 | 64 + 5G → A | – | – | + | |||
| 2 | 2 | 2 | 64 + 2T>G | – | – | – | |||
| 1 | 2 | 2 | 1386-1387delGT | – | – | + | |||
| 1 | 1 | 1 | 550-2A>G | – | – | + | |||
| 2 | 2 | – | 1791 + 2T>G | – | – | – | |||
| IFNGR1 | AR | 2 | 3 | 2 | c.131delC | – | + | –a | |
| CMC | STAT1 (GOF) | AD | 1 | 1 | 1 | c.876T4G | L163R | – | + |
| 1 | 1 | – | c.820C>T | R274W | – | – | |||
aThese mutations have been already reported for the first time in other patients from Tunisian origin.
XL, X-linked inheritance; AR, autosomal recessive inheritance; AD, autosomal dominant inheritance; SCID, severe combined immunodeficiencies; ALPS, autoimmune lymphoproliferative syndrome; AID, activation-induced cytidine deaminase; CGD, chronic granulomatous disease; MSMD, Mendelian susceptibility to mycobacterial disease; LAD, leukocyte adhesion deficiency; CMC, chronic mucocutaneous candidiasis; PID, primary immunodeficiency; MHC, major histocompatibility complex; LAD I, leukocyte adhesion deficiency type 1; HIGM, hyper-IgM syndrome; HIES, hyper-IgE syndrome.