Clinical phenotype of XMEN patients
| . | Patient . | ||||||
|---|---|---|---|---|---|---|---|
| A.2 . | C.1 . | A.1 . | D.1 . | E.1 . | F.1 . | B.1* . | |
| Age, y | 3 | 4 | 7 | 16 | 16 | 23 | 45 |
| Age at death, y | 23 | 45 | |||||
| MAGT1 mutation | |||||||
| Genomic | g.46668_46677del 10 | g.25009G>A | g.46668_46677del 10 | g.29684C>T | g.43183delC | g.46604G>T | g.29684C>T |
| cDNA | c.859_997del139 | c.172G>A | c.859_997del139 | c.409C>T | c.598delC | c.859_997del139 | c.409C>T |
| Protein | p.Asn287*fs*1 | p.Trp37* | p.Asn287*fs*1 | p.Arg137* | p.Arg200Glyfs*13 | p.Asn287*fs*1 | p.Arg137* |
| Recurrent infections | |||||||
| Epstein-Barr virus | + | + | + | + | + | + | + |
| Herpes simplex virus | + | – | + | – | – | – | – |
| Viral pneumonia | + | – | + | – | – | – | – |
| Otitis media | + | – | + | – | + | + | – |
| Sinusitis | + | + | + | – | – | – | – |
| Streptococcal pharyngitis | – | – | – | + | – | + | – |
| Epiglottitis | – | – | – | + | – | – | – |
| Molluscum contagiosum | – | – | – | – | + | – | – |
| Varicella + recurrent zoster | – | – | – | – | – | + | – |
| Pertussis | – | – | – | – | – | + | – |
| Cancer | |||||||
| Lymphoma | None | None | None | B-cell LPD† | Burkitt’s‡§ | Hodgkin§ | Lymphoma |
| Age at onset, y | 12 | 7, 14 | 17, 22 | 45 | |||
| Vaccination titer | |||||||
| Tetanus toxoid | + | + | – | N/D | + | +/− | N/D |
| Haemophilus influenzae type B | + | N/D | + | N/D | N/D | N/D | N/D |
| Diphtheria | N/D | N/D | + | N/D | + | +/− | N/D |
| Pneumococcal | +/− | + | + | N/D | – | – | N/D |
| Peripheral blood cells, % (range) | |||||||
| T cells | 61.2 (53-75) | N/D | 54.3 (53-75) | 48.6 (53-75) | 53.6 (53-75) | 69 (55-83) | 83.9 (57.3-86.4) |
| CD4 T cells | 27.8 (32-51) | N/D | 13.5 (28-47) | 19.1 (31-47) | 17 (31-47) | 40 (28-57) | 74.4 (28.6-57.2) |
| CD8 T cells | 20.8 (14-30) | N/D | 22.4 (16-30) | 43 (18-35) | 34 (18-35) | 34 (10-39) | 8.6 (12.9-46.9) |
| CD4:CD8 | 0.7 (0.9-3.7) | 0.6 (0.9-3.4) | 0.6 (1.4-1.7) | 0.55 (0.9-3.4) | 0.5 (0.9-3.4) | 1.1 (1.0-3.6) | 8.5 (1.0-3.6) |
| B cells | 26.9 (16-35) | N/D | 37.1 (14-33) | 46 (13-27) | 0 (RITX) | 44 (6-23) | 14.1 (6-23) |
| NK cells | 15 (3-15) | N/D | 5.4 (4-17) | 5 (3-22) | 7 (3-22) | 11 (3-22) | 1.7 (4.6-29.8) |
| Eosinophils | 1.85 (0-4.1) | N/D | 1.2 (0-4.7) | 1.5 (0.8-7) | 1.2 (0.8-7) | 1 (0.8-7) | 0.2 (0.8-7) |
| Neutrophils | 8 (22.4-69) | N/D | 20.4 (28.6-74.5) | 37.9 (28.6-74.5) | 55 (28.6-74.5) | 34 (34-67.9) | 88.2 (34-67.9) |
| Monocytes | 8.1 (4.2-12.2) | N/D | 9.7 (4.2-12.3) | 13 (4.2-12.3) | 9.9 (4.2-12.3) | 7 (4.2-12.3) | 3.4 (4.2-12.3) |
| Immunoglobulinlevels (range) | |||||||
| IgG, mg/dL | 286 (424-1051) | 1030 (620-1300) | 1160 (633-1280) | 1690 (639-1349) | 611 (639-1349) | 619 (639-1349) | 734 (642-1730) |
| IgA, mg/dL | 7 (14-23) | 56 (50-200) | 87 (25-154) | 14.8 (45-236) | 35.6 (45-236) | 29.9 (70-312) | 128 (91-499) |
| IgM, mg/dL | 55 (48-1680) | 115 (60-200) | 92 (43-1960) | 29 (56-352) | 87 (56-352) | 38 (56-352) | 14 (34-342) |
| IgE, IU/mL | 2000 (310-2950) | N/D | 1750 (1070-6890) | 2100 (206-1952) | 1500 (206-1952) | 5 (1.53-114) | 5 (0-90) |
| . | Patient . | ||||||
|---|---|---|---|---|---|---|---|
| A.2 . | C.1 . | A.1 . | D.1 . | E.1 . | F.1 . | B.1* . | |
| Age, y | 3 | 4 | 7 | 16 | 16 | 23 | 45 |
| Age at death, y | 23 | 45 | |||||
| MAGT1 mutation | |||||||
| Genomic | g.46668_46677del 10 | g.25009G>A | g.46668_46677del 10 | g.29684C>T | g.43183delC | g.46604G>T | g.29684C>T |
| cDNA | c.859_997del139 | c.172G>A | c.859_997del139 | c.409C>T | c.598delC | c.859_997del139 | c.409C>T |
| Protein | p.Asn287*fs*1 | p.Trp37* | p.Asn287*fs*1 | p.Arg137* | p.Arg200Glyfs*13 | p.Asn287*fs*1 | p.Arg137* |
| Recurrent infections | |||||||
| Epstein-Barr virus | + | + | + | + | + | + | + |
| Herpes simplex virus | + | – | + | – | – | – | – |
| Viral pneumonia | + | – | + | – | – | – | – |
| Otitis media | + | – | + | – | + | + | – |
| Sinusitis | + | + | + | – | – | – | – |
| Streptococcal pharyngitis | – | – | – | + | – | + | – |
| Epiglottitis | – | – | – | + | – | – | – |
| Molluscum contagiosum | – | – | – | – | + | – | – |
| Varicella + recurrent zoster | – | – | – | – | – | + | – |
| Pertussis | – | – | – | – | – | + | – |
| Cancer | |||||||
| Lymphoma | None | None | None | B-cell LPD† | Burkitt’s‡§ | Hodgkin§ | Lymphoma |
| Age at onset, y | 12 | 7, 14 | 17, 22 | 45 | |||
| Vaccination titer | |||||||
| Tetanus toxoid | + | + | – | N/D | + | +/− | N/D |
| Haemophilus influenzae type B | + | N/D | + | N/D | N/D | N/D | N/D |
| Diphtheria | N/D | N/D | + | N/D | + | +/− | N/D |
| Pneumococcal | +/− | + | + | N/D | – | – | N/D |
| Peripheral blood cells, % (range) | |||||||
| T cells | 61.2 (53-75) | N/D | 54.3 (53-75) | 48.6 (53-75) | 53.6 (53-75) | 69 (55-83) | 83.9 (57.3-86.4) |
| CD4 T cells | 27.8 (32-51) | N/D | 13.5 (28-47) | 19.1 (31-47) | 17 (31-47) | 40 (28-57) | 74.4 (28.6-57.2) |
| CD8 T cells | 20.8 (14-30) | N/D | 22.4 (16-30) | 43 (18-35) | 34 (18-35) | 34 (10-39) | 8.6 (12.9-46.9) |
| CD4:CD8 | 0.7 (0.9-3.7) | 0.6 (0.9-3.4) | 0.6 (1.4-1.7) | 0.55 (0.9-3.4) | 0.5 (0.9-3.4) | 1.1 (1.0-3.6) | 8.5 (1.0-3.6) |
| B cells | 26.9 (16-35) | N/D | 37.1 (14-33) | 46 (13-27) | 0 (RITX) | 44 (6-23) | 14.1 (6-23) |
| NK cells | 15 (3-15) | N/D | 5.4 (4-17) | 5 (3-22) | 7 (3-22) | 11 (3-22) | 1.7 (4.6-29.8) |
| Eosinophils | 1.85 (0-4.1) | N/D | 1.2 (0-4.7) | 1.5 (0.8-7) | 1.2 (0.8-7) | 1 (0.8-7) | 0.2 (0.8-7) |
| Neutrophils | 8 (22.4-69) | N/D | 20.4 (28.6-74.5) | 37.9 (28.6-74.5) | 55 (28.6-74.5) | 34 (34-67.9) | 88.2 (34-67.9) |
| Monocytes | 8.1 (4.2-12.2) | N/D | 9.7 (4.2-12.3) | 13 (4.2-12.3) | 9.9 (4.2-12.3) | 7 (4.2-12.3) | 3.4 (4.2-12.3) |
| Immunoglobulinlevels (range) | |||||||
| IgG, mg/dL | 286 (424-1051) | 1030 (620-1300) | 1160 (633-1280) | 1690 (639-1349) | 611 (639-1349) | 619 (639-1349) | 734 (642-1730) |
| IgA, mg/dL | 7 (14-23) | 56 (50-200) | 87 (25-154) | 14.8 (45-236) | 35.6 (45-236) | 29.9 (70-312) | 128 (91-499) |
| IgM, mg/dL | 55 (48-1680) | 115 (60-200) | 92 (43-1960) | 29 (56-352) | 87 (56-352) | 38 (56-352) | 14 (34-342) |
| IgE, IU/mL | 2000 (310-2950) | N/D | 1750 (1070-6890) | 2100 (206-1952) | 1500 (206-1952) | 5 (1.53-114) | 5 (0-90) |
+/–, positive for some serotypes and negative for others; LPD, lymphoproliferative disease; N/D, not determined. RITX, rituximab; adapted from Chaigne-Delalande.5
Lymphocyte numbers in peripheral blood were measured a few months prior to death but before chemotherapy and transplantation.
EBV-positive B-cell LPD in the central nervous system.
B-cell lymphomas of two different restrictions: first λ light chain and then κ light chain; no MYC/IGH gene rearrangements were found.
Presumably two independent lymphomas based on the timing of onset.