Sequence analysis, immune status, and clinical findings in patients with HIGM due to mutations of AID, NEMO, UNG, and Btk
. | . | . | . | Age, y . | . | Immunoglobulins (mg/dL) . | . | . | Absolute counts, per mm3 . | . | Lymphocyte subsets, per mm3 . | . | . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient no./sex . | gDNA mutation, nucleotide . | Predicted effect on protein . | Exon . | Onset . | Now . | IgM . | IgG . | IgA . | Neutrophil . | Lymphocyte . | CD4 . | CD8 . | CD19 . | Lymphocyte proliferation mitogens/antigens* . | Clinical findings . | ||||||
| AID | |||||||||||||||||||||
| 78/M | 259T > C | Cys B7 Arg | 3 | 1.6 | 4 | 437 (43-207) | <33 | <7 | 5582 | 5832 | 1982 | 1341 | 175 | N/D | Recurrent sinopulmonary infections, chronic diarrhea, cervical lymph node hyperplasia | ||||||
| 79/F | 292T > G† | Leu 98 Arg | 3 | 4 | 25 | 640 (43-207) | 40 | 24 | 3124 | 3110 | 1555 | 212 | 196 | N/N | Recurrent sinopulmonary infections, cervical lymph node hyperplasia, adenitis with abscess formation | ||||||
| 80/M | 334C > T | Arg 112 Cys | 3 | 1.3 | 12 | 1820 (43-207) | <33 | 29 | 6875 | 1860 | 668 | 428 | 353 | N/D | Staphylococcal arthritis and osteomyelitis, consanguinity | ||||||
| 81/M | 334C > T | Arg 112 Cys | 3 | 2 | 7 | 1220 (43-207) | <33 | <7 | 6386 | 2141 | 771 | 299 | 792 | N/D | Cervical lymph node hyperplasia, atypical mycobacteria, bronchioctasis, consanguinity | ||||||
| UNG | |||||||||||||||||||||
| 82/M | 497-498 del AT | fs, stop at 159 | 2 | 15 | 39 | 785 (56-352) | 209 | <6.7 | 5687 | 3568 | 1268 | 687 | 549 | NA/D | Recurrent sinopulmonary infections, chronic epididymitis, pulmonary lymphoid hyperplasia, Sjógren syndrome, consanguinity | ||||||
| NEMO | |||||||||||||||||||||
| 83/M | 1426 ins C | fs, stop at 393 | 10 | 0.03 | 1.2 | 41 (27-101) | 109 | <6 | 6245 | 10 414 | 8022 | 2392 | 2533 | N/N | EDA, recurrent sinopulmonary infections, abdominal wall abscess, gram-negative sepsis, meningitis, chronic diarrhea, persistent molluseum contagiosum, failure to thrive | ||||||
| Btk | |||||||||||||||||||||
| 84/M | 338A > T | Lys 199 stop | 8 | 3 | 4 | 42 (43-207) | <7 | <7 | 1840 | 3950 | 2805 | 909 | 40 (122-632) | N/N | Neutropenia, impetigo, osteomyelitis, mandibular abscess due to atypical mycobacteria | ||||||
| 85a/M | 1984A > G | Arg 618 Gly | 18 | 9 | 11 | 73 (43-207) | 130 | <7 | 6897 | NA | NA | NA | NA | N/N | Recurrent sinopulmonary infections, chronic diarrhea, pocumococcal meningitis | ||||||
| 85b/M | 1984A > G | Arg 618 Gly | 18 | 10 | 13 | 58 (43-207) | 199 | <7 | 5894 | 5264 | 3368 | 1579 | 526 (122-632) | N/N | Recurrent sinopulmonary infections | ||||||
. | . | . | . | Age, y . | . | Immunoglobulins (mg/dL) . | . | . | Absolute counts, per mm3 . | . | Lymphocyte subsets, per mm3 . | . | . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient no./sex . | gDNA mutation, nucleotide . | Predicted effect on protein . | Exon . | Onset . | Now . | IgM . | IgG . | IgA . | Neutrophil . | Lymphocyte . | CD4 . | CD8 . | CD19 . | Lymphocyte proliferation mitogens/antigens* . | Clinical findings . | ||||||
| AID | |||||||||||||||||||||
| 78/M | 259T > C | Cys B7 Arg | 3 | 1.6 | 4 | 437 (43-207) | <33 | <7 | 5582 | 5832 | 1982 | 1341 | 175 | N/D | Recurrent sinopulmonary infections, chronic diarrhea, cervical lymph node hyperplasia | ||||||
| 79/F | 292T > G† | Leu 98 Arg | 3 | 4 | 25 | 640 (43-207) | 40 | 24 | 3124 | 3110 | 1555 | 212 | 196 | N/N | Recurrent sinopulmonary infections, cervical lymph node hyperplasia, adenitis with abscess formation | ||||||
| 80/M | 334C > T | Arg 112 Cys | 3 | 1.3 | 12 | 1820 (43-207) | <33 | 29 | 6875 | 1860 | 668 | 428 | 353 | N/D | Staphylococcal arthritis and osteomyelitis, consanguinity | ||||||
| 81/M | 334C > T | Arg 112 Cys | 3 | 2 | 7 | 1220 (43-207) | <33 | <7 | 6386 | 2141 | 771 | 299 | 792 | N/D | Cervical lymph node hyperplasia, atypical mycobacteria, bronchioctasis, consanguinity | ||||||
| UNG | |||||||||||||||||||||
| 82/M | 497-498 del AT | fs, stop at 159 | 2 | 15 | 39 | 785 (56-352) | 209 | <6.7 | 5687 | 3568 | 1268 | 687 | 549 | NA/D | Recurrent sinopulmonary infections, chronic epididymitis, pulmonary lymphoid hyperplasia, Sjógren syndrome, consanguinity | ||||||
| NEMO | |||||||||||||||||||||
| 83/M | 1426 ins C | fs, stop at 393 | 10 | 0.03 | 1.2 | 41 (27-101) | 109 | <6 | 6245 | 10 414 | 8022 | 2392 | 2533 | N/N | EDA, recurrent sinopulmonary infections, abdominal wall abscess, gram-negative sepsis, meningitis, chronic diarrhea, persistent molluseum contagiosum, failure to thrive | ||||||
| Btk | |||||||||||||||||||||
| 84/M | 338A > T | Lys 199 stop | 8 | 3 | 4 | 42 (43-207) | <7 | <7 | 1840 | 3950 | 2805 | 909 | 40 (122-632) | N/N | Neutropenia, impetigo, osteomyelitis, mandibular abscess due to atypical mycobacteria | ||||||
| 85a/M | 1984A > G | Arg 618 Gly | 18 | 9 | 11 | 73 (43-207) | 130 | <7 | 6897 | NA | NA | NA | NA | N/N | Recurrent sinopulmonary infections, chronic diarrhea, pocumococcal meningitis | ||||||
| 85b/M | 1984A > G | Arg 618 Gly | 18 | 10 | 13 | 58 (43-207) | 199 | <7 | 5894 | 5264 | 3368 | 1579 | 526 (122-632) | N/N | Recurrent sinopulmonary infections | ||||||