Table 2.
Phenotype and genotype of CGD patients and their relatives.
| N° | Patients | NBT test % positive cells | Cyt C reduction nmol/min/106cells | DHR stimulation index* | Western blot or flow cytometry | Nucleotide | Gene location | Amino-acid change | Protein domain | CGD sub-type |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | H5 m | 0 | 0 | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| 2 | H3 f† | / | / | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| H1 f† | / | / | / | / | / | / | / | AR670 ? | ||
| H2 f (sister) | 93 | 14.8 | / | Pres p67phox | Not carrier | |||||
| H4 f (sister) | 94 | 13.1 | / | Pres p67phox | Not carrier | |||||
| Father | 95 | 13.9 | / | Pres p67phox | Carrier | |||||
| Mother | 96 | 15.6 | / | Pres p67phox | Carrier | |||||
| 3 | M2 m | 0 | 0 | Abs p67phox | c.505 C>G and deletion of exon 6 | c.609+372_670-655 | p.Gln169Glu and del. Exon 6 | Activation domain | AR670, New mutation | |
| M1 f (sister) | / | / | / | Pres p67phox | Carrier | |||||
| M3 m (brother) | 98 | / | / | Pres p67phox | / | |||||
| Father | / | 3.4 | / | Pres p67phox | Carrier | |||||
| Mother | / | 4.2 | / | Pres p67phox | Carrier | |||||
| 4 | N4 f | 0 | 0 | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| 5 | N5 m† | / | 0 | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| 6 | N6 f | 0 | / | / | / | / | / | / | / | AR670 |
| N1 f (sister) | / | / | / | Pres p67phox | Not carrier | |||||
| N2 f (sister) | / | / | / | Pres p67phox | Not carrier | |||||
| N3 f (sister) | / | / | / | Pres p67phox | Carrier | |||||
| Father | 54 | 10.4 | / | Pres p67phox | Carrier | |||||
| Mother | 85 | 10.3 | / | Pres p67phox | Carrier | |||||
| 7 | O3 m | / | / | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| O1 m (twin) | / | / | / | Pres p67phox | Carrier | |||||
| O2 m (twin) | / | / | / | Pres p67phox | Carrier | |||||
| Father | / | / | / | Pres p67phox | Carrier | |||||
| Mother | / | / | / | Pres p67phox | Carrier | |||||
| 8 | P1 f | / | 0 | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| P2 f (sister) | / | 7.6 | / | Pres p67phox | Carrier | |||||
| P3 m (brother) | / | / | / | Pres p67phox | Not carrier | |||||
| Father | / | 4.8 | / | Pres p67phox | Carrier | |||||
| Mother | / | / | / | Pres p67phox | Carrier | |||||
| 9 | Q3 m (twin) | 0 | 0 | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| Q1 m (brother) | 91 | 5.7 | / | Pres p67phox | Not carrier | |||||
| Q2 m (brother) | 95 | 5.9 | / | Pres p67phox | Not carrier | |||||
| Q4 f (twin) | 90 | 5.7 | / | Pres p67phox | Carrier | |||||
| Father | 91 | 4.2 | / | Pres p67phox | Carrier | |||||
| Mother | 93 | 4.4 | / | Pres p67phox | Carrier | |||||
| 10 | R9 m | 0 | Abs NOX2 | c252 G>T, del exon 3 | CYBB- exon 3 | p.Ser48_Ala84del | II-TM and B-Loop | X910CGD | ||
| R5 m † | / | / | / | / | / | / | / | / | X910CGD ? | |
| Mother | / | 3.8 | / | Pres NOX2 | Carrier | |||||
| 11 | S11 m | / | 0 | / | Abs p22phox | c.268C>T | CYBA- exon 4 | p. Arg90Trp | C-term | AR220 |
| S8 m† | / | / | / | / | / | / | / | / | AR220 ? | |
| Father | / | 19.0 | / | Pres p22phox | Carrier | |||||
| Mother | / | / | / | Pres p22phox | Carrier | |||||
| 12 | T2 m | 0 | / | / | Abs p47phox | c.579G>A | NCF1- exon 7 | p.Trp193* | SH3-1 domain | AR470 |
| T1 f (sister) | 95 | / | / | Pres p47phox | Carrier | |||||
| T3 m (brother) | 93 | / | / | Pres p47phox | Carrier | |||||
| Father | 95 | / | / | Pres p47phox | Carrier | |||||
| Mother | 98 | / | / | Pres p47phox | Carrier | |||||
| 13 | W5 f | / | / | / | Abs p22phox | c.295_301delGTGCCCG | CYBA- exon 5 | p.Val99Profs*90 | TM | AR220 |
| W3 f (sister) | / | / | / | Pres p22phox | Not carrier | |||||
| Father | / | / | / | Pres p22phox | Carrier | |||||
| Mother | / | / | / | Pres p22phox | Carrier | |||||
| 14 | X4 m | / | / | / | Abs p47phox | c.579G>A | NCF1- exon 7 | p.Trp193* | SH3-1 domain | AR470 |
| 15 | X5 f | / | / | / | Abs p47phox | c.579G>A | NCF1- exon 7 | p.Trp193* | SH3-1 domain | AR470 |
| X2 f (sister) | / | / | / | Pres p47phox | Not carrier | |||||
| X3 f (sister) | / | / | / | Pres p47phox | Carrier | |||||
| Father | / | / | / | Pres p47phox | Carrier | |||||
| Mother | / | / | / | Pres p47phox | Carrier | |||||
| 16 | Y3 f | / | / | / | Abs p47phox | c.75_76delGT | NCF1- exon 2 | p.Tyr26Hisfs*26 | PX domain | AR470 |
| Father | / | / | / | Pres p47phox | Carrier | |||||
| 17 | Z7 f (twin) | 0 | / | 1.0 | Abs p22phox | c.295_301delGTGCCCG | CYBA- exon 5 | p.Val99Profs*90 | TM | AR220 |
| 18 | Z1 f †$ | 0 | / | / | Abs p22phox | c.295_301delGTGCCCG | CYBA- exon 5 | p.Val99Profs*90 | TM | AR220 |
| Z6 m† | / | / | / | / | / | / | / | AR220 ? | ||
| Z4 m† | / | / | / | / | / | / | / | AR220 ? | ||
| Z8 f (twin) | / | / | / | Pres p22phox | Carrier | |||||
| Z2 m (brother) | / | / | / | Pres p22phox | Carrier | |||||
| Z3 m (brother) | / | / | / | Pres p22phox | Not carrier | |||||
| Father | / | / | / | Pres p22phox | Carrier | |||||
| Mother | / | / | / | Pres p22phox | Carrier | |||||
| 19 | AB1 m | / | / | 1.3 | Abs p47phox | c.579G>A | NCF1- exon 7 | p.Trp193* | SH3-1 domain | AR470 |
| 20 | AB2 m | / | / | 1.3 | Abs p47phox | c.579G>A | NCF1- exon 7 | p.Trp193* | SH3-1 domain | AR470 |
| 21 | AD9 f† | / | / | 1.0 | Abs p67phox | c.229C>T | NCF2 - exon 2 | p.Arg77* | TPR domain | AR670 |
| AD1 m† | / | / | / | / | / | / | / | / | AR670 ? | |
| AD3 m† | / | / | / | / | / | / | / | / | AR670 ? | |
| AD4 f† | / | / | / | / | / | / | / | / | AR670 ? | |
| AD5 f† | / | / | / | / | / | / | / | / | AR670 ? | |
| AD2 f (sister) | / | / | / | Pres p67phox | Not carrier | |||||
| Father | / | / | / | Pres p67phox | Carrier | |||||
| 22 | AH4 f† | / | / | 1.0 | Abs p22phox | c.295_301delGTGCCCG | CYBA-exon 5 | p.Val99Profs*90 | TM | AR220 |
| Father | / | / | / | Pres p22phox | Carrier | |||||
| Mother | / | / | / | Pres p22phox | Carrier | |||||
| 23 | AI4 f | / | / | 1.0 | Abs p22phox | c.295_301delGTGCCCG | CYBA- exon 5 | p.Val99Profs*90 | TM | AR220 |
| 24 | AI6 f† | 0 | / | / | / | / | / | / | / | AR220 |
| AI3 f† | / | / | / | / | / | / | / | / | AR220 ? | |
| Father | / | / | 35.4 | Pres p22phox | Carrier | |||||
| Mother | / | / | 21.3 | Pres p22phox | Carrier | |||||
| 25 | AJ2 f | / | / | 1.0 | Abs p22phox | c.295_301delGTGCCCG | CYBA- exon 5 | p.Val99Profs*90 | TM | AR220 |
| AJ1 f | / | / | / | / | / | / | / | / | AR220 ? | |
| Father | / | / | 49.6 | Pres p22phox | Carrier | |||||
| Mother | / | / | 44.6 | Pres p22phox | Carrier | |||||
| 26 | AK4 f | / | / | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| 27 | AK3 f† | 0 | / | / | / | / | / | / | / | AR670 |
| Father | / | / | / | Pres p67phox | Carrier | |||||
| Mother | / | / | / | Pres p67phox | Carrier | |||||
| 28 | AM2 m† | / | / | 1.0 | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| AM1m (brother) | / | / | / | Pres p67phox | Carrier | |||||
| AM3 f (sister) | / | / | / | Pres p67phox | Carrier | |||||
| AM4 f (sister) | / | / | / | Pres p67phox | Not carrier | |||||
| Father | / | / | / | Pres p67phox | Carrier | |||||
| Mother | / | / | / | Pres p67phox | Carrier | |||||
| 29 | AN2 m | / | / | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| 30 | AN3 m† | / | / | / | Abs p67phox | c.1171_1175delAAGCT | NCF2- Exon 12 | p.Lys391Glufs*9 | PB1 domain | AR670 |
| 31 | AN1 f† | 0 | / | / | / | / | / | / | / | AR670 |
| Mother | / | / | / | Pres p67phox | Carrier | |||||
| Normal values (n = 100) | 90 ± 6 | 11.3 ± 3.3 | >5 (98 ± 2) | / | / | / | / | / | / |
*
Stimulation Index (SI): MFI of activated neutrophils/MFI of resting neutrophils.
$
Patient Z1 was diagnosed in Germany (NBT test and genetic test). We consider a patient to have CGD when he or she has been diagnosed by a NBT test and the clinical signs are suggestive of CGD (N6, AI6, AK3, and AN1).
?Means that the patient exhibited a clinical profile compatible with CGD but no biological diagnosis was done before his death and he has a CGD patient in his family (H1, R5, S8, Z4, Z6, AD1, AD3, AD4, AD5, AI3, and AJ1).
†
means that the patient died; / means not determined; m, male; f, female; Normal values were obtained from 100 donors; Abs, absent; Pres, present; protein expression was performed by western blotting or by flow cytometry as described in Patients and Methods.
Blue for AR67 CGD, green for X91 CGD, pink for AR22 CGD and pale orange for AR47 CGD. New mutations are in bold.