Table 2.
Phenotypical and genotypical profiles of the 16 X91‐CGD patients
| Patients | NBT test % of positive cells | Cyt c Red O2 ‐ nmol/min/106cells a | Resorufin H2O2 nmol/min/106cells b | DHR, index (% of cells) c | Protein expression flow cytometry index (% of cells) or WB | Cyt b 558 picomol/mg proteins | cDNA nucleotide change | Gene location | Amino‐acid change | CGD‐type |
|---|---|---|---|---|---|---|---|---|---|---|
| Standard values (n=100) | 90 ± 6 | 11.3 ± 3.3 | 25.7 ± 10.3 | > 5 | 40 ± 13 | 166 ± 30 | – | – | – | – |
| P1 | – | – | – | 2.3 (98)–277 (2) | 1.0 (98)–25·1 (2) | – | –67 delT | Promoter | No | X91– |
| M1 | – | – | – | 4.3 (36)–22.3 (63) | 1.0 (33)–17·1 (67) | – | Carrier | |||
| P2 | – | – | – | 1.1 (100) | 1.1 (100) | – | c.39delT | Exon 1 | p.Phe13LeufsX21 | X910 |
| M2 | – | – | – | 2.6 (47)–47.0 (53) | 1.0 (46)–18.9 (54) | – | Carrier | |||
| Gm2 | – | – | – | – | – | – | Mutation not found | Not carrier | ||
| P3 | 1.0 | – | 0 | 1.0 (100) | Abs NOX2 | – | c.201dupT | Exon 3 | p.Leu68SerfsX34 | X910 |
| P4a | 21.0 | – | – | 10.4 (100) | 2.3 (100) | 36 | c.253–1879A>G | Intron 3 | Skip exon 3, p.Cys85LeufsX32 | X91– |
| M4 | 80 | – | – | 3.4 (16)–13.4 (84) | 2.8 (10)–30.0 (90) | 342 | Carrier | |||
| S4 | 58 | – | – | 1.2 (47)–12.4 (53) | 2.2 (37)–30.0 (63) | 315 | Carrier | |||
| P5 | 0 | – | – | 1.0 (100) | 1.0 (100) | – | c.600_603dupTTAC | Exon 6 | p.Phe202LeufsX2 | X910 |
| M5 | 30 | – | – | 8.4 (78)–49.8 (22) | 1.0 (65)–55.0 (35) | – | Carrier | |||
| Am5 | 72 | – | – | 2.1 (24)–6.9 (76) | 1.0 (17)–9.3 (83) | – | Carrier | |||
| Gam5 | – | – | – | – | – | – | Mutation not found | Not carrier | ||
| P6 | 0 | 0 | 0 | – | – | 0 | c.623 C>G and c.1508 C>T | Exon 6 and Exon 12 | p.Thr208Arg and Thr503Ile | X910 |
| M6 | 39 | 5.5 | 10.4 | – | – | 76 | Carrier | |||
| Am6 | – | – | – | – | – | – | Mutation not found | Not carrier | ||
| P7 | 0 | 1.3 (100) | 1.3 (100) | c.674+3G>T | Intron 6 | Deletion of exon 6 or exon 5 and 6, p.Asp162ThrfsX15 | X910 | |||
| M7 | 94 | – | – | 57.8 (100) | 44.7 (100) | – | Not carrier | |||
| P8 | 0 | – | – | 1.0 (100) | 1.2 (100) | – | c.676C>T | Exon 7 | p.Arg226X | X910 |
| M8 | 49 | – | – | 39.0 (48)–154 (52) | 1.2 (49)–19.0 (51) | – | Carrier | |||
| S8 d | 94 | – | – | 15.5 (100) | 8.3 (100) | – | – | ND d | ||
| P9 | 0 | – | – | 1.0 (100) | 1.0 (100) | – | c.816G>A | Exon 8 | p.Trp272X | X910 |
| M9 | 36 | – | – | 2.8 (78)–25.0 (22) | 1.0 (60)–23.0 (40) | – | Carrier | |||
| Am9 | 90 | – | – | 158 (100) | 12 (100) | – | Mutation not found | Not carrier | ||
| Am9' | 96 | – | – | 97 (100) | 20 (100) | – | Mutation not found | Not carrier | ||
| Gam9 | – | – | – | 63 (100) | 10 (100) | – | Mutation not found | Not carrier | ||
| P10 | – | – | – | 1.0 (100) | 1.0 (100) | – | c.980T>A | Exon 9 | Val327Asp | X910 |
| M10 | – | – | – | 46.0 (58)–244 (42) | 1.0 (64)–23.0 (46) | – | Carrier | |||
| P11 | 0 | – | – | 1.0 (100) | 1.0 (100) | – | c.1061_1065delATATC | Exon 9 | p.His354ProfsX16 | X910 |
| M11 | 12 | – | – | 3.5 (93)–217 (7) | 1.3 (90)–44.7 (10) | – | Carrier | |||
| P12 | 0 | 0 | – | – | Abs NOX2 | 0 | c.897+1258_1151+129del (del of 1657bp) | Intron 9–exon 9 | Skip exon 9, p.Val300AspfsX4 | X910 |
| M12 | 57 | 1.9 | – | – | NOX2 diminished | 39 | Carrier | |||
| S12 | 73 | 5.0 | – | – | NOX2 diminished | 55 | Carrier | |||
| B12 d | 80 | 10.0 | – | – | 103 | ND d | ||||
| P13 | 2 | – | – | – | Abs NOX2 | – | c. 1166G>A | Exon 10 | p.Gly389Glu | X910 |
| P14 | 4 | – | 0 | – | Abs NOX2 | – | c.1167_1179delGCCCTTTGGCACT | Exon 10 | p.Phe391ValfsX9 | X910 |
| D14 | 48 | – | – | – | – | Carrier | ||||
| P15 | 0 | 0 | – | – | Pres NOX2 | – | c.1235G>A | Exon 10 | p.Gly412Glu | X91+ |
| M15 | 88 | 14.6 | – | – | – | – | Carrier | |||
| Am15 | – | – | – | – | – | – | Mutation not found | Not carrier | ||
| P16 | 4 | – | – | 1.1 (100) | 1.2 (100) | – | c.1546T>C | Exon 12 | p.Trp516Arg | X910 |
| M16 | 36 | – | – | 42 (68)–189 (32) | 2.0 (69)–35.9 (31) | – | Carrier |
P = patient; M = mother; Gm = grandmother; S = sister; B = brother; D = daughter; Am = maternal aunt; Gam = maternal grand‐aunt.
a
Activation with PMA;
b
activation with PMA;
c
MFI of activated cells/MFI resting cells (% of cells having index) or Western blot results; Abs = absence; Pres = presence; Decr = decrease;
d
genetic analysis not performed because they were safe and not of age.
Patients with new mutations are shown in bold type.
DHR = dihydrorhodamine; CGD = chronic granulomatous disease; NOX2 = nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2; – = not determined; PMA = phorbol myristate acetate; MFI = mean fluorescence intensity.