Table 1.
Patients’ clinical and laboratory characteristics
| Family 6 | Family 7 | Family 8 | Family 12 | ||||
|---|---|---|---|---|---|---|---|
| Patient | 6.1 | 6.2 | 7.1 | 7.2 | 8 | 12.1 | 12.2 |
| Gender | M | F | M | M | F | M | M |
| Consanguinity | No | No | No | No | No | No | No |
| Age of first presentation (months) | 3 | NA | NA | 6–7 | 8 | 3 | NA |
| Age at diagnosis (months) | 10 | 0 | 0 | 8 | 8 | 8 | 0 |
| Diagnostic trigger | Failure to thrive | Family history | Family history | Recurrent infections | Failure to thrive, respiratory infection, lymphopenia | Recurrent infections, failure to thrive | Family history |
| Infections pre diagnosis | Candida, viral gastroenteritis | None | None | RSV bronchio-litis, persistent rotavirus, candida, PJP | RSV, PJP | Recurrent URTI, para-influenza type I, persistent candida | None |
| Other problems | Persistent diarrhea | None | None | Failure to thrive, encephalopathy | None | Possible encephalitis | None |
| Age at BMT (months) | 12 | 1 | 2 | NA | 11 | 8 and 12 | 2 |
| Status | Alive | Alive | Alive | Died pre transplant | Alive | Died 115 days post second transplant | Alive |
| Serum immunoglobulins at diagnosis (g/l) (normal ranges according to the Harriet Lane Handbook 19th edition) | |||||||
| IgG | 8.1 (2.9–10.7) | 10.4 (6.4–16.1) | 8.7 (6.4–16.1) | 3 (2.2–9.0) | <0.4 (2.2–9.0) | <0.33 (2.2–9.0) | 10.5 (6.4–16.1) |
| IgA | 0.23 (0.16–0.84) | <0.01 (0.01–0.04) | <0.3 (0.01–0.04) | 0.12 (0.11–0.90) | <0.3 (0.11–0.90) | <0.07 (0.11–0.90) | <0.07 (0.01–0.04) |
| IgM | 1.71 (0.41–1.49) | 0.18 (0.06–0.25) | <0.22 (0.06–0.25) | 1.15 (0.34–1.26) | <0.19 (0.34–1.26) | <0.2 (0.34–1.26) | 0.17 (0.06–0.25) |
| Lymphocyte subpopulations (cells/mm3) (normal ranges according to Comans-Bitter, J Pediatr 1997) | |||||||
| CD3 | 185 (1600–6700) | 0 (600–5000) | 0 (600–5000) | 0 (2400–6900) | 0 (2400–6900) | 10 (2400–6900) | 0 (600–5000) |
| CD4 | 42 (1000–4600) | 0 (400–3500) | 0 (400–3500) | 0 (1400–5100) | 0 (1400–5100) | 0 (1400–5100) | 0 (400–3500) |
| CD8 | 144 (400–2100) | 0 (200–1900) | 0 (200–1900) | 0 (600–2200) | 0 (600–2200) | 0 (600–2200) | 0 (200–1900) |
| CD19 | 227 (600–2700) | 24 (40–1100) | 39 (40–1100) | 1395 (700–2500) | 362 (700–2500) | 250 (700–2500) | 627 (40–1100) |
| NK | 52 (200–1200) | 23 (100–1900) | 832 (100–1900) | 71 (100–1000) | 161 (100–1000) | ND | 697 (100–1900) |
| Lymphocyte proliferation (cpm) [SI] | |||||||
| Patient PHA (control) | No response (ND) | 217 [−] (49370 [117x]) | ND | 2336 [1x] (95381 [521x]) | ND | 138 [0.9x] (32003 [89x]) | 511 [0.3x] (95069 [211x]) |
| ConA | 97 (1824) | ND | ND | ND | ND | ND | ND |
| PWM | 131 (4337) | ND | ND | ND | ND | ND | ND |
| Genetic analysis | |||||||
| Prior to WES | No | Targeted PID panel | IL7R Sanger sequencing | No | IL7R Sanger sequencing | No | No |
| Results | NA | Het. IL7R c.221+2T>G | Het. IL7R p.Q26X | NA | Het. IL7R c.221+2T>G | NA | NA |
| WES | No | Yes | No | Yes | Yes | No | Yes |
| Results | NA | Het. Ex3del + het. c.221+2T>G | NA | Het. Ex2_4del + het. p.Q26X | Het. Ex3del + het. c.221+2T>G | NA | Het. Ex3del + intronic SNVs |
ConA concanavalin A, Het. heterozygous, NA not applicable, ND not determined, PHA phytohemagglutinin, PJP pneumocystis jiroveci pneumonia, PWM poke weed mitogen, RSV respiratory syncytial virus, SI stimulation index (cpm of stimulated/cpm of unstimulated cells), URTI upper respiratory tract infection