Table 4.

Sequence analysis, immune status, and clinical findings in patients with HIGM due to mutations of AID, NEMO, UNG, and Btk

Age, yImmunoglobulins (mg/dL)Absolute counts, per mm3Lymphocyte subsets, per mm3
Patient no./sexgDNA mutation, nucleotidePredicted effect on proteinExonOnsetNowIgMIgGIgANeutrophilLymphocyteCD4CD8CD19Lymphocyte 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
  • Values in parentheses indicate normal values for age, according to individual laboratories.

    N indicates normal; D, decrease; NA, not available; EDA, ectodermal dysplasia; fs, frameshift.

  • * Mitogens are PHA, PMA, or ConA: antigens are tetanus candida, diphtheria.

  • Novel mutation, not yet reported.