TABLE I.
Clinical and genetic information of patients with RAG2 deficiency
| Clinical phenotype | Autoimmunity/inflammation | Infections/malignancy | Patient no. | Mutation | Age | ALC (cells/μL) | CD3 (cells/μL) | CD19 (cells/μL) | CD16/56 (cells/μL) | References |
|---|---|---|---|---|---|---|---|---|---|---|
| CID-G/AI (n = 3) | Aplastic anemia; granulomas in spleen, lungs, and skin; ITP; neutropenia; splenomegaly | ARDS, disseminated and vaccine-associated varicella, meningitis, pneumonia, sinusitis, infections with Cryptococcus species, EBV, and RSV | P1 | a. T77N; b. G451A | 2 y | 769–1,554 | 538–1,057 | 54–202 | 131–355 | 5 |
| P2 | a. G451A; b. M459L | 9 mo | 480 | 138 | 12 | 86 | 28 | |||
| P3 | a-b. F62L | 5 y | 687 | 391 | 78 | 215 | 28 | |||
| AS (n = 7) | AIHA, alopecia areata, APS, biliary cirrhosis, granulomas in skin and bone marrow, hepatomegaly, IBD, ITP, neutropenia, splenomegaly, psoriasis, polyarthritis | Bronchiectasis, cholecystitis, chronic diarrhea, DIC, fungal nail infections, hyper-IgM syndrome, jaundice, Klebsiella species, meningitis, molluscum, oral thrush, otitis media, PJP, pneumonia, Pseudomonas species sepsis, rhinorrhea, skin rash-papules and abscesses, vaccine, associated varicella, RSV, CMV, and EBV viremia | P4 | a-b. M459L | 4 mo | NA | 691 | 173 | 657 | 26 |
| P5 | a. R73H; b. P180H | 13 mo | 1,479 | 401 | 524 | 654 | ||||
| P6 | a-b. G35A | 7 mo | 1,027 | 716 | 105 | 209 | 28 | |||
| P7 | a-b. G35A | 10 mo | 1,108 | 13 | 276 | |||||
| P8 | a-b. G35A | 12 mo | 2,700 | 717 | 131 | 898 | ||||
| P9 | a. G35A; b. E437K | 5 mo | 3,460 | 1,384 | 62 | 1,176 | ||||
| P10 | a-b. E407X | 18 y | 3,480 | 2,750 | 0 | 661 | 28 | |||
| OS (n = 28) | AIHA, eczema erythroderma, generalized edema, hepatomegaly, hepatosplenomegaly, lymphadenopathy, seborrhea-like dermatitis, splenomegaly | BCGitis, chronic diarrhea, CMV infection, failure to thrive, LAD, interstitial pneumonia, myocarditis, onychomycosis, recurrent chest infection and URTI, PJP, prolonged rotavirus infection, Pseudomonas pneumonia, Staphylococcus aureus skin infection, sepsis, severe infections | P11 | a.K440N; b.P253R | 7 mo | 792 | 103 | 8 | 657 | 17 |
| P12 | a. S160L; b. M502V | 3 wk | 9,064 | 7,250 | 0 | 1,360 | 17 | |||
| P13 | a-b. T215I | NA | 600 | 240 | 0 | 198 | 16 | |||
| P14 | a-b. M459L | 4 mo | 869 | 149 | 4 | 279 | 26 | |||
| P15 | a. C41W; b. M285R | 1 wk | 5,880 | 2,646 | 1 | 2,470 | 4 | |||
| P16 | a.C41W; b.M285R | 0 mo | 660 | 554 | <6 | 66 | ||||
| P17 | a-b. A456T | 0 mo | 45,000 | 41,000 | 0 | NA | 23 | |||
| P18 | a. Q278X; b. R73H | 0 mo | 8,339 | 7,071 | 0 | NA | 25 | |||
| P19 | a-b. R229W | 0 mo | 280 | 162 | 17 | 53 | 4 | |||
| P20 | a-b. R229W | 4 mo | 77 | 4 | 2 | 4 | ||||
| P21 | a-b. R229W | 4 mo | NA | 61 | 2 | 19 | 4 | |||
| P22 | a-b. R229W | NA | 287 | 46 | 6 | 184 | 16 | |||
| P23 | a-b. R229W | NA | 1,972 | 1,045 | 39 | 375 | 16 | |||
| P24 | a-b. R229W | 15 d | 889 | 595 | 4 | 231 | 17 | |||
| P25 | a. R229W; b.G95R | NA | 1,953 | 1,074 | 78 | 19 | 16 | |||
| P26 | a. G95R; b. W453R | <5 mo | 10,000 | 5,200 | 204 | NA | 22 | |||
| P27 | a-b. R229Q | 2 wk | 8,600 | 3,698 | <86 | 3,956 | 4, 24 | |||
| P28 | a.R39G; b.R229Q | 2 mo | 10,000 | 7,400 | 0 | NA | 14 | |||
| P29 | a. R229Q; b. locus del | 2.5 mo | 322 | 113 | 16 | 161 | 2, 4 | |||
| P30 | a-b. E480X | NA | 11,000 | 2,778 | 0 | 3,740 | 19 | |||
| P31 | a.G95R; b.E480X | 3 mo | 11,000 | 2,871 | 0 | 3,800 | 27 | |||
| P32 | a-b. I444M | 3 mo | 620 | 415 | <6 | 180 | 18 | |||
| P33 | a-b. W416L | 3 mo | 34,000 | 31,647 | 0 | 1,347 | 17 | |||
| P34 | a.-b. W453R | NA | NA | NA | NA | NA | 15 | |||
| P35 | a-b. G35V | NA | 1,850 | 537 | 130 | 370 | 16 | |||
| P36 | a-b. M443I | 1 mo | 5,700 | 2,354 | 11 | NA | 25 | |||
| P37 | a-b. G157V | NA | 5,600 | 4,592 | 56 | 504 | 19 | |||
| P38 | a-b. G35V | 4 mo | 1,320 | 488 | 0 | 500 | 27 | |||
| SCID (n = 20) | Eczema, erythroderma, lymphadenopathy, hepatosplenomegaly might be present in patients with maternal T-cell engraftment | BCGitis, diarrhea, failure to thrive, oral ulcers, oral thrush, oral candidiasis pneumonia, protracted diarrhea, respiratory distress | P39† | a-b. N474S | 1 wk | 1,120 | 22 | 1 | 784 | 4 |
| P40 | a-b. R229W | NA | 110 | 40 | 0 | 45 | 16 | |||
| P41 | a-b. R229W | 1 mo | 1,076 | 126 | 1 | 869 | ||||
| P42 | a-b. R229W | NA | NA | NA | NA | NA | 21 | |||
| P43 | a-b. R229W | NA | NA | NA | NA | NA | 21 | |||
| P44 | a-b.T215I & R229Q | 12 d | 684 | 5 | 7 | 382 | 20 | |||
| P45 | a. R39G; b. R229Q | NA | NA | 0 | 0 | NA | 13 | |||
| P46 | a-b. D65Y | NA | 400 | 16 | 8 | 228 | 19 | |||
| P47 | a-b. Q16X | NA | NA | NA | NA | NA | 15 | |||
| P48 | a-b. G35V | NA | 576 | 110 | 0 | 432 | 16 | |||
| P49 | a-b. G35V | NA | 290 | 9 | 0 | 159 | 16 | |||
| P50 | a-b. G35V | NA | NA | 0 | 0 | NA | 14 | |||
| P51 | a-b. G35V | 3 mo | NA | NA | NA | NA | 17 | |||
| P52 | a-b. R41W | 6 mo | NA | 5 | 1 | 804 | ||||
| P53 | a-b. C478Y | NA | NA | 0 | 0 | NA | 2 | |||
| P54 | a-b. W307X | 4 mo | 720 | <7 | <7 | 533 | 4 | |||
| P55 | a-b. C478Y | 0 mo | 2,000 | 80 | <20 | 820 | 4 | |||
| P56† | a-b. C478Y | 2 wk | 5,000 | 3,500* | <50 | 2,050 | 2, 4 | |||
| P57 | a-b. K127X | 5 mo | 810 | NA | <8 | 760 | 18 | |||
| P58 | a-b. K127X | 1 mo | 978 | <10 | <10 | 918 | 18 |
Age, Age at presentation; AIHA, autoimmune hemolytic anemia; ALC, absolute lymphocyte count; APS, antiphospholipid syndrome; ARDS, acute respiratory distress syndrome; BCGitis, systemic dissemination of the attenuated Mycobacterium bovis bacillus of the tuberculosis vaccine; CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; IBD, inflammatory bowel disease; ITP, immune thrombocytopenic purpura; LAD, lymphadenopathy; NA, not available; N, normal; PJP, Pneumocystis jirovecii pneumonia; RSV, respiratory syncytial virus; URTI, urinary tract infection.
*
Maternal.
†
Maternal engraftment.