Table 1.
Allele 1 | Allele 2 | Protein | Age at diagnosis |
Infections | Autoimmunity/ Lymphoproliferation |
Malignancy | Immunology | Radiosensitivity | Reference |
---|---|---|---|---|---|---|---|---|---|
SCID | |||||||||
c.47T>C | c.356C>G | I16T; S119* | 1mo | LRI, oral thrush | T−B−NK+ | sensitive | 20 | ||
c.82G>C | c.82G>C | A28P | T−B−NK+ | sensitive | 11 | ||||
c.95C>T | del Ex 1-3 | S32F | 19 | ||||||
c.95C>G | 2N/A | S32C | 1 | ||||||
c.110A>G | c.110A>G | D37G | 2mo | moniliasis, gastroenteritis | T−B−NK+ | sensitive | 4 | ||
c.241C>T | c.241C>T | R81* | 9 | ||||||
c.281delC | c.281delC | S94fs*2 | TmatB−NK+ | 11 | |||||
c.353G>T | c.353G>T | G118V | 5mo | LRI, PJP, CMV | T−B−NK+ | sensitive | 22 | ||
c.353G>T | c.353G>T | G118V | T−B−NK+ | 11 | |||||
c.362T>C | del Ex 1-3 | M121T | 8mo | LRI | T−B−NK+ agamma | unpublished | |||
c.404G>A | c.404G>A | G135E | 4mo | VZV | sensitive | 22 | |||
c.493G>A | c.493G>A | D165N | 3 | ||||||
c.494A>T | c.494A>T | D165V | T−B−NK+ | 11 | |||||
c.571C>T | N/A | R191* | unpublished | ||||||
c.597C>A | c.597C>A | Y199* | oral and genital ulcers | 10 | |||||
c.682C>A | c.682C>A | H228N | T−B−NK+ | sensitive | 11 | ||||
c.716delC | c.716delC | P239Lfs*46 | 8mo | recurrent URI, oral thrush, chronic diarrhea | T−B−NK+ | unpublished | |||
c.761A>T | c.309delG (splice site) | H254L; K103fs | 25 | ||||||
c.781delG | c.781delG | A261Qfs*24 | 9 | ||||||
c.1050delA | c.1050delA | V381Lfs*5 | T−B−NK+ | 11 | |||||
c.1140_1146delAGTTCAC | c.1140_1146delAGTTCAC | V383Efs*19 | TmatB−NK+ | sensitive | 11 | ||||
c.1147C>T | c.1147C>T | R383* | TmatB−NK+ | 11 | |||||
c.1167_1168insAG | c.delEx3 | D390Rfs*13 | 2mo | URI | T−B−NK+ hypogam | sensitive | 26 | ||
c.1179delT | c.1179delT | F393Lfs*9 | 3mo | LRI, PJP, oral thrush, CMV | T−B−NK+ hypogam | sensitive | 20 | ||
c.1391_1395delGAATC | c.1391_1395delGAATC | G464Afs*18 | 1mo | LRI, GI | T−B−NK+ | sensitive | 4 | ||
Omenn Syndrome | |||||||||
c.2T>C | c.103C>G | M1T; H35D | 5mo | sepsis, BCG | alopecia, erythrodermia, lymphadenopathy, hepato/splenomegaly, granuloma | lymphoma | ThiB−NK+ hypogam TCR repertoire 25% of WT |
sensitive | 13 |
Leaky SCID | |||||||||
c.1A>C | c.401C>G | M1V; T134R | 6mo | pharyngitis, stomatitis, gastroenteritis | T−B−NK+ | unpublished | |||
c.19C>T | c.457G>A | Q7*; G153R | 73% CD3 3% CD19 of MNC in BM |
19 | |||||
c.194C>T | N/A | T65I | 18mo | pulmonary TB | T−B−NK+ | unpublished | |||
c.211A>C | del Ex 1-3 | T71P | 10mo (onset) | URI, Pseudomonas soft tissue infection | AIHA, neutropenia, thrombocytopenia, lymphadenopathy hepato/splenomegaly | TloBloNK+ low IgA and IgG2; absent response to vaccine (Hib and tetanus); proliferation to PHA initially normal, later absent | 21 | ||
c.211A>C | del Ex 1-3 | T71P | birth | URI, oral candidiasis | AIHA | TloB−NK+ low IgG, absent IgA; decreased TRECs; poliferation to PHA initially normal, later absent | 21 | ||
c.207_209delGTT | c.377G>A | L70del; G126D | 4.5y | URI, Candida | AIHA | TloB+NK+ hypogam no specific Ab response | sensitive | 23 | |
c.400A>G | del Ex 1+ (not specified) | T134A | lymphadenopathy | Tlo, polyclonal T cells, proliferation to PHA >30% of normal | unpublished | ||||
c.512C>G | c.insInt2b | P171R | 27y | Candida, HPV, fungal brain abscess | neutropenia, thrombocytopenia | bilateral carcinoma in situ of nipples | TloBloNK+ abnormal T cell proliferation | mildly sensitive | 24 |
c.512C>G | c.1299_1306dupAGGATGCT | P171R; C436* | 7y | URI, LRI | lymphadenopathy, granulomatous inflammation | Hodgkin lymphoma | TloB−NK+ absent IgA | 24 | |
c.1290_1306delACAAACCCCAGGATGCT | c.1290_1306delACAAACCCCAGGATGCT | T432fs*16 | 4y | LRI, GI | cholangitis and liver cirrhosis (died at 16y) | TloBlo hypogam | 27 | ||
c.1353_1359delTTGTGAA | c.delEx1-3 | D451Kfs*11 | birth | LRI, Candida | AIHA, ITP, cervical lymphadenopathy | lymphoma (9mo) | T−B−NK+ monoclonal IgG, absent IgA | 27 | |
c.1353_1359delTTGTGAA | c.delEx1-3 | D451Kfs*11 | birth | LRI, Candida | lymphoma | TloBlo hypogam | 27 | ||
c.1353_1359delTTGTGAA | c.delEx1-3 | D451Kfs*11 | 1y | URI, LRI, CNS Toxo | TloB−NK+ hypogam | sensitive | 27 | ||
c.1464delG | c.1464delG | Q488fs | 1mo | URI, LRI, CMV | oral ulcers, sclerosing cholangitis, thrombocytopenia, hepatosplenomegaly | TloB−NK+ LGL cells, hypogam | 28 |
Ab, antibody; agamma, agammaglobulinemia; AIHA, autoimmune hemolytic anemia; BCG, Bacillus Calmette-Guérin; BM, bone marrow; CMV, cytomegalovirus; CNS, central nervous system; GI, gastrointestinal infection; HPV, human papillomavirus; hypogam, hypogammaglobulinemia; ITP, idiopathic thrombocytopenic purpura; LGL, large granular lymphocytes; LRI, lower respiratory infections; MNC, mononuclear cells; N/A, not available; PJP, Pneumocystis jirovecii pneumonia; PHA, phytohemagglutinin; TB, Tuberculosis; TCR, T cell receptor; Tmat, maternal T cells; Toxo, Toxoplasmosis; TRECs, T cell receptor excision circles; URI, upper respiratory infection; VZV, varicella zoster virus