Clinical and laboratory features of 5 infants with hypomorphic RAG mutations
| . | Patient no. . | ||||
|---|---|---|---|---|---|
| 1 . | 2 . | 3 . | 4 . | 5 . | |
| Gene mutations | RAG1 deletion (encompassing also RAG2); M435V* | RAG2G139R*; G139R* | RAG1 G392E*; L732fs | RAG1R332X; R561H* | RAG1L526R, S117fs |
| VDJ recombination activity, % of wild type† | nd | 1.5 | 1.5 | nd | nd |
| Age at onset | First month | 6 mo | Birth | 5 mo | 2 mo |
| Erythrodermia/pachydermia | + | + | + | − | + |
| Liver/spleen enlargement | − | − | + | − | + |
| Lymphadenopathy | − | − | + | − | − |
| Diarrhea | + | + | + | + | − |
| Edemas | + | − | + | − | − |
| Infections | Achromoacter xylosoxidans sepsis | Pneumonia, sepsis | Candida, Klebsiella | Candida, Pseudomonas | Interstitial pneumonia |
| ALC, cells ×10−9/L | 62.3 | 0.3 | 3.7 | 0.4 | 25.7 |
| CD3, % | 96 | 20.9 | 83.9 | 47.4 | 91 |
| CD4, % | 32 | 10.4 | 69.6 | 19.0 | 77 |
| CD8, % | 62 | 9.0 | 12.9 | 6.3 | 10 |
| CD19, % | 0 | 1.1 | 0.4 | 0.1 | 0 |
| CD16, % | 2 | 60.0 | 15.6 | 42.7 | 4 |
| CD4+ CD45R0+/CD4+, % | nd | 82.3 | 96.0 | 85.8 | 100 |
| Response to PHA, cpm ×10−3 | 39.2 (179) | 1.6 (121) | 8.0 (134) | 6.5 (112) | 9.4 (57) |
| IgG, g/L | 0.41 | <1.0 | 1.21 | 0.14 | 2.40 |
| IgA, g/L | <0.07 | <0.05 | <0.06 | 0.06 | 0.10 |
| IgM, g/L | <0.04 | <0.05 | <0.25 | 0.04 | 0.24 |
| IgE, kU/L | 128 | nd | nd | <19 | >5000 |
| . | Patient no. . | ||||
|---|---|---|---|---|---|
| 1 . | 2 . | 3 . | 4 . | 5 . | |
| Gene mutations | RAG1 deletion (encompassing also RAG2); M435V* | RAG2G139R*; G139R* | RAG1 G392E*; L732fs | RAG1R332X; R561H* | RAG1L526R, S117fs |
| VDJ recombination activity, % of wild type† | nd | 1.5 | 1.5 | nd | nd |
| Age at onset | First month | 6 mo | Birth | 5 mo | 2 mo |
| Erythrodermia/pachydermia | + | + | + | − | + |
| Liver/spleen enlargement | − | − | + | − | + |
| Lymphadenopathy | − | − | + | − | − |
| Diarrhea | + | + | + | + | − |
| Edemas | + | − | + | − | − |
| Infections | Achromoacter xylosoxidans sepsis | Pneumonia, sepsis | Candida, Klebsiella | Candida, Pseudomonas | Interstitial pneumonia |
| ALC, cells ×10−9/L | 62.3 | 0.3 | 3.7 | 0.4 | 25.7 |
| CD3, % | 96 | 20.9 | 83.9 | 47.4 | 91 |
| CD4, % | 32 | 10.4 | 69.6 | 19.0 | 77 |
| CD8, % | 62 | 9.0 | 12.9 | 6.3 | 10 |
| CD19, % | 0 | 1.1 | 0.4 | 0.1 | 0 |
| CD16, % | 2 | 60.0 | 15.6 | 42.7 | 4 |
| CD4+ CD45R0+/CD4+, % | nd | 82.3 | 96.0 | 85.8 | 100 |
| Response to PHA, cpm ×10−3 | 39.2 (179) | 1.6 (121) | 8.0 (134) | 6.5 (112) | 9.4 (57) |
| IgG, g/L | 0.41 | <1.0 | 1.21 | 0.14 | 2.40 |
| IgA, g/L | <0.07 | <0.05 | <0.06 | 0.06 | 0.10 |
| IgM, g/L | <0.04 | <0.05 | <0.25 | 0.04 | 0.24 |
| IgE, kU/L | 128 | nd | nd | <19 | >5000 |
Values of proliferative response to PHA in healthy controls are indicated in parentheses.
ALC indicates absolute lymphocyte count; PHA, phytohemagglutinin; +, present; −, not present; and nd, not detected.
Morphic mutations.
For patients 2 and 3, V(D)J recombination activity was evaluated using a plasmid-based colony formation assay, as described.14