BTK Expression Status in XLA Patients and Mothers as Evaluated by a Flow Cytometric Assay
| Family . | BTK Mutations . | BTK Expression in Monocytes of Patients . | Pattern of BTK Expression in Monocytes of Mothers . | Family History . |
|---|---|---|---|---|
| Missense mutation | ||||
| 1 (P23)* | Arg28 → Pro (PH)† | 4.5%‡ | Mosaic (56.4)§ | (−) |
| 2 (P32) | Gly302 → Glu (SH2) | 23.2% | Mosaic (53.1) | (+) |
| 3∥ | Leu358 → Phe (SH2) | 32.0% | Mosaic (13.5) | (+) |
| 4 (P5) | Cys502 → Trp (SH1) | 8.9% | Mosaic (47.7) | (−) |
| 5 (P6) | Cys502 → Trp (SH1) | 0.2% | Mosaic (64.4) | (+) |
| 6 (P17) | Asp521 → His (SH1) | 97.2% | Single (95.4) | (−) |
| 7 (P14) | Phe644 → Ser (SH1) | 5.8% | Mosaic (61.7) | (+) |
| Nonsense mutation | ||||
| 8 (P20) | Trp124 → Stop (PH) | 0.1% | Mosaic (29.8) | (−) |
| 9 (P24) | Tyr134 → Stop (PH) | 0.3% | Mosaic (84.8) | (+) |
| 10 (P19) | Gln196 → Stop (TH) | 0.2% | Mosaic (62.5) | (−) |
| 11¶ | Trp281 → Stop (SH2) | 0.9% | Mosaic (80.9) | (+) |
| 12 (P22) | Tyr425 → Stop (SH1) | 0.4% | Mosaic (25.1) | (+) |
| 13 (P1) | Glu441 → Stop (SH1) | 0.1% | Mosaic (37.8) | (+) |
| 14 (P10) | Gln459 → Stop (SH1) | 0.5% | Single (99.2) | (−) |
| 15 (P2) | Gln497 → Stop (SH1) | 0.1% | Single (95.0) | (−) |
| 16 (P27) | Trp634 → Stop (SH1) | 0.2% | Mosaic (50.7) | (+) |
| Deletion | ||||
| 17 (P11) | Large deletion at the 3′ terminal half | 0.7% | Single (96.0) | (−) |
| 18 (P21) | 23-bp deletion (PH) → FS (stop)** | 0.1% | Mosaic (16.8) | (−) |
| 19 (P13) | 5-bp deletion (PH) → FS (stop) | 0.5% | Mosaic (56.3) | (+) |
| 20 (P26) | 5-bp deletion (PH) → FS (stop) | 0.1% | Mosaic (76.2) | (−) |
| 21¶ | 4-bp deletion (TH) → FS (stop) | 0.2% | Mosaic (24.9) | (−) |
| 22 (P15) | 136-bp deletion (SH3) → FS (stop) | 0.3% | Mosaic (59.2) | (+) |
| 23 (P4) | 426-bp deletion (SH2, 3) → Truncated | 0.3% | Single (97.5) | (−) |
| 24 (P8) | 1-bp deletion (SH1) → FS (stop) | 0.4% | Mosaic (49.8) | (+) |
| 25 (P9) | 342-bp deletion (SH1) → Truncated | 0.2% | Mosaic (34.7) | (−) |
| 26 (P28) | 65-bp deletion (SH1) → FS (stop) | 0.5% | Mosaic (66.2) | (+) |
| 27 (P3) | 10-bp deletion (SH1) → FS (stop) | 0.3% | Mosaic (37.1) | (−) |
| 28¶ | Large deletion in the SH1 domain | 0.1% | Mosaic (25.2) | (−) |
| Insertion | ||||
| 29 (P31) | 60-bp insertion (SH1) → Stop | 0.2% | Mosaic (61.5) | (+) |
| 30¶ | 4-bp insertion (SH1) → Stop | 0.1% | Mosaic (14.5) | (+) |
| Multiple alteration | ||||
| 31 (P34) | Tyr142 → Stop (PH) | 0.3% | Mosaic (48.8) | (+) |
| Exon-11 skipping | ||||
| Exon-15 and -16 skipping | ||||
| No mutation in the coding region but reduced levels of BTK transcripts | ||||
| 32 (P7) | 0.1% | Mosaic (61.3) | (−) | |
| 33 (P29) | 0.1% | Mosaic (50.2) | (+) | |
| 34 (P30) | 0.2% | Mosaic (57.1) | (+) | |
| 35 (P33) | 0.1% | Mosaic (31.4) | (+) | |
| Not performed for the genetic analysis | ||||
| 36 | 0.3% | Mosaic (68.4) | (−) | |
| 37 | 0.1% | Mosaic (29.1) | (−) | |
| 38 | 0.4% | Mosaic (61.2) | (−) | |
| 39 | 0.8% | Mosaic (56.7) | (−) | |
| 40 | 0.2% | Mosaic (81.5) | (−) | |
| 41 | 0.1% | Single (98.7) | (−) | |
| Normal controls (N = 32) | 97.0% ± 2.5%†† | Single |
| Family . | BTK Mutations . | BTK Expression in Monocytes of Patients . | Pattern of BTK Expression in Monocytes of Mothers . | Family History . |
|---|---|---|---|---|
| Missense mutation | ||||
| 1 (P23)* | Arg28 → Pro (PH)† | 4.5%‡ | Mosaic (56.4)§ | (−) |
| 2 (P32) | Gly302 → Glu (SH2) | 23.2% | Mosaic (53.1) | (+) |
| 3∥ | Leu358 → Phe (SH2) | 32.0% | Mosaic (13.5) | (+) |
| 4 (P5) | Cys502 → Trp (SH1) | 8.9% | Mosaic (47.7) | (−) |
| 5 (P6) | Cys502 → Trp (SH1) | 0.2% | Mosaic (64.4) | (+) |
| 6 (P17) | Asp521 → His (SH1) | 97.2% | Single (95.4) | (−) |
| 7 (P14) | Phe644 → Ser (SH1) | 5.8% | Mosaic (61.7) | (+) |
| Nonsense mutation | ||||
| 8 (P20) | Trp124 → Stop (PH) | 0.1% | Mosaic (29.8) | (−) |
| 9 (P24) | Tyr134 → Stop (PH) | 0.3% | Mosaic (84.8) | (+) |
| 10 (P19) | Gln196 → Stop (TH) | 0.2% | Mosaic (62.5) | (−) |
| 11¶ | Trp281 → Stop (SH2) | 0.9% | Mosaic (80.9) | (+) |
| 12 (P22) | Tyr425 → Stop (SH1) | 0.4% | Mosaic (25.1) | (+) |
| 13 (P1) | Glu441 → Stop (SH1) | 0.1% | Mosaic (37.8) | (+) |
| 14 (P10) | Gln459 → Stop (SH1) | 0.5% | Single (99.2) | (−) |
| 15 (P2) | Gln497 → Stop (SH1) | 0.1% | Single (95.0) | (−) |
| 16 (P27) | Trp634 → Stop (SH1) | 0.2% | Mosaic (50.7) | (+) |
| Deletion | ||||
| 17 (P11) | Large deletion at the 3′ terminal half | 0.7% | Single (96.0) | (−) |
| 18 (P21) | 23-bp deletion (PH) → FS (stop)** | 0.1% | Mosaic (16.8) | (−) |
| 19 (P13) | 5-bp deletion (PH) → FS (stop) | 0.5% | Mosaic (56.3) | (+) |
| 20 (P26) | 5-bp deletion (PH) → FS (stop) | 0.1% | Mosaic (76.2) | (−) |
| 21¶ | 4-bp deletion (TH) → FS (stop) | 0.2% | Mosaic (24.9) | (−) |
| 22 (P15) | 136-bp deletion (SH3) → FS (stop) | 0.3% | Mosaic (59.2) | (+) |
| 23 (P4) | 426-bp deletion (SH2, 3) → Truncated | 0.3% | Single (97.5) | (−) |
| 24 (P8) | 1-bp deletion (SH1) → FS (stop) | 0.4% | Mosaic (49.8) | (+) |
| 25 (P9) | 342-bp deletion (SH1) → Truncated | 0.2% | Mosaic (34.7) | (−) |
| 26 (P28) | 65-bp deletion (SH1) → FS (stop) | 0.5% | Mosaic (66.2) | (+) |
| 27 (P3) | 10-bp deletion (SH1) → FS (stop) | 0.3% | Mosaic (37.1) | (−) |
| 28¶ | Large deletion in the SH1 domain | 0.1% | Mosaic (25.2) | (−) |
| Insertion | ||||
| 29 (P31) | 60-bp insertion (SH1) → Stop | 0.2% | Mosaic (61.5) | (+) |
| 30¶ | 4-bp insertion (SH1) → Stop | 0.1% | Mosaic (14.5) | (+) |
| Multiple alteration | ||||
| 31 (P34) | Tyr142 → Stop (PH) | 0.3% | Mosaic (48.8) | (+) |
| Exon-11 skipping | ||||
| Exon-15 and -16 skipping | ||||
| No mutation in the coding region but reduced levels of BTK transcripts | ||||
| 32 (P7) | 0.1% | Mosaic (61.3) | (−) | |
| 33 (P29) | 0.1% | Mosaic (50.2) | (+) | |
| 34 (P30) | 0.2% | Mosaic (57.1) | (+) | |
| 35 (P33) | 0.1% | Mosaic (31.4) | (+) | |
| Not performed for the genetic analysis | ||||
| 36 | 0.3% | Mosaic (68.4) | (−) | |
| 37 | 0.1% | Mosaic (29.1) | (−) | |
| 38 | 0.4% | Mosaic (61.2) | (−) | |
| 39 | 0.8% | Mosaic (56.7) | (−) | |
| 40 | 0.2% | Mosaic (81.5) | (−) | |
| 41 | 0.1% | Single (98.7) | (−) | |
| Normal controls (N = 32) | 97.0% ± 2.5%†† | Single |
*Parentheses indicate the patient number designated in a prior study.18
Domains of BTK involving mutations.
Data indicate the percentages of anti–BTK-stained cells exceeding the upper limit of the control staining with the isotype-matched irrelevant MoAb.
The percentages of cells expressing BTK normally.
∥A case that was previously reported.28
¶Patients whose mutations had been analyzed in another report.27
FS (stop), frame shift resulting in secondary premature termination.
Means ± SD.