Table 1.

Clinical and genetic summary of patients with TCF3 deficiency

Pt.	Inheritance	Variant	Zygosity	Mechanism	Ethnicity	Sex	Age	Onset	Infections	Other findings	CD19+B cells (/µL) / (% of lymphocytes)	Hypo/Agammaglobulinemia	IgG (g/L)	IgA (g/L)	IgM (g/L)	Ref.
1	AR	c.808 C>T p.Q270*	Homo	LOF	Tunisian	M	10 years	Early childhood	Recurrent pneumonia and meningitis	Facial dysmorphic features, B-ALL	NA / 0.1	Yes	NA	NA	NA	[22]
2	AR	c.808 C>T p.Q270*	Homo	LOF	Tunisian	F	13 years	Early childhood	Recurrent pneumonia	Facial dysmorphic features, failure to thrive	NA / 3.5	Yes	6.75	0.67	0.18	[22]
3	AR	Exons 5–11 deletion	Homo	LOF	NA	F	9 years	1 year	Recurrent pneumonia, chronic diarrhea	Anemia, failure to thrive	49 / 1.2	Yes	1.11	< 0.15	0.14	[23]
4	AR	c.380 C>G p.S127*	Homo	LOF	Iranian	F	32 years	7 years	Recurrent otitis, sinusitis, pneumonia, herpetic encephalitis	Mild hearing loss due to herpetic encephalitis	0 / 0.2	Yes	4.30	0.07	0.22	[24]
5	AR	c.1451–18 A>T p.G486Lfs*4	Homo	LOF	NA	M	6 years	NA	Recurrent pneumonia	Facial dysmorphic features, B-ALL	0 / 0	Yes	1.37	0.07	0.32	[21]
6	AR	c.1451–18 A>T p.G486Lfs*4	Homo	LOF	NA	M	3 years	NA	No	Facial dysmorphic features	116 / 2.5	Yes	2.95	0.12	0.11	[21]
7	AR	c.1451–18 A>T p.G486Lfs*4	Homo	LOF	NA	F	8 months	NA	No	Facial dysmorphic features, B-ALL	210 / 3.0	Yes	2.30	0.31	0.12	[21]
8	AR	c.1326 + 5 G>A p.L442_V443ins27	Homo	LOF	NA	F	7 years	NA	Bacteremic pneumococcal pneumonia, EBV-associated leukocytosis with lymphocytosis	Facial dysmorphic features, mild intellectual disability	396 / 8.2	Yes	7.52a	0.27	0.17	[21]
9	AD	c.808 C>T p.Q270*	Hetero	HI	Tunisian	M	49 years	No	No	No	NA / 1.9	No	8.91	3.21	0.21	[22]
10	AD	c.808 C>T p.Q270*	Hetero	HI	Tunisian	F	49 years	No	No	No	NA / 2.0	No	10.23	1.13	0.59	[22]
11	AD	c.808 C>T p.Q270*	Hetero	HI	Tunisian	M	10 years	No	No	No	NA / 2.4	No	9.25	1.51	0.37	[22]
12	AD	c.380 C>G p.S127*	Hetero	HI	Iranian	M	NA	No	No	No	NA	NA	NA	NA	NA	[24]
13	AD	c.380 C>G p.S127*	Hetero	HI	Iranian	F	NA	No	No	No	NA	NA	NA	NA	NA	[24]
14	AD	c.380 C>G p.S127*	Hetero	HI	Iranian	M	NA	No	No	No	NA	NA	NA	NA	NA	[24]
15	AD	c.1451–18 A>T p.G486Lfs*4	Hetero	HI	NA	M	26 years	No	No	No	175 / 5.3	No	12.62	3.12	0.45	[21]
16	AD	c.1451–18 A>T p.G486Lfs*4	Hetero	HI	NA	F	23 years	No	No	No	50 / 7.0	Yes	7.26	0.39	0.35	[21]
17	AD	c.1541 C>A p.S514*	Hetero	HI	NA	M	10 years	NA	Varicella, impetigo, oral thrush, gastroenteritis	No	136 / 4.1	Yes	9.01a	0.28	0.18	[21]
18	AD	c.599_600delinsGCT p.Y200Cfs*54	Hetero	HI	NA	F	53 years	NA	Recurrent and chronic sinus infection	Asthma, granulomatous lung disease, obesity, type 2 diabetes, diabetes insipidus	124 / 8.7	Yes	4.86	1.62	0.10	[21]
19	AD	c.1326 + 5 G>A p.V433*	Hetero	HI	NA	F	32 years	No	No	Cholecystectomy	366 / 10.8	NA	NA	NA	NA	[21]
20	AD	c.1739del p.D580Afs*29	Hetero	HI	NA	F	62 years	NA	Recurrent sinusitis, impaired vaccination response to pneumococcus	No	204 / 5.7	Yes	5.60	1.30	0.30	[21]
21	AD	c.1451–18 A>G p.0	Hetero	HI	NA	F	27 years	NA	Pneumonia, bronchitis	Vitiligo	166 / 4.8	Yes	3.90	0.70	0.30	[21]
22	AD	Chr19: 959,646–1,649,320 p.0	Hetero	HI	NA	F	6 years	NA	Recurrent respiratory infections	Crohn’s disease, early onset IBS, Peutz‒Jeghers syndrome, mild motor and intellectual developmental delay	76 / 2.7	Yes	6.46	0.43	0.11	[21]
23b	AD	c.503_504insC p.T168Tfs*24	Hetero	HI	NA	F	61 years	Teenage years	Meningitis, chronic diarrhea, recurrent respiratory infections, impaired vaccination response to pneumococcus, diphtheria, tetanus	Hashimoto’s thyroiditis, SLE	NA / NA ↓	Yes	4.50	0.20	0.20	[25]
24	AD	c.503_504insC p.T168Tfs*24	Hetero	HI	NA	M	35 years	NA	Sinusitis, chronic tonsillitis, impaired vaccination response to pneumococcus, diphtheria, tetanus	Type 1 diabetes, seronegative arthritis, synovitis	NA/NA ↓	Yes	5.50	< 0.07	0.40	[25]
25	AD	c.1663 G>A p.E555K	Hetero	DN	North Americans of European	F	34 years	9 months	Pneumococcal meningitis	No	NA / 0.4	Yes	8.59a	< 0.07	< 0.07	[18, 19]
26	AD	c.1663 G>A p.E555K	Hetero	DN	North Americans of European	F	8 years	10 months	Recurrent otitis	Eosinophilic dermatitis	NA / 2.5	Yes	< 0.33	0.14	< 0.07	[18, 19]
27	AD	c.1663 G>A p.E555K	Hetero	DN	North Americans of European	M	15 years	2 years	Vaccine-associated polio	Hepatomegaly	NA / 0.2	Yes	8.44a	< 0.01	0.10	[18, 19]
28	AD	c.1663 G>A p.E555K	Hetero	DN	Mexican	M	20 years	4 years	Recurrent otitis and arthritis	No	NA / 1.5	Yes	< 1.00	< 0.05	< 0.05	[18, 19]
29	AD	c.1663 G>A p.E555K	Hetero	DN	British	F	35 years	11 months	Streptococcus pneumoniae pneumonia and empyema, intermittent sinusitis, Haemophilus influenzae conjunctivitis	No	2 / 0.2	Yes	< 0.50	< 0.07	< 0.10	[20]
30	AD	c.1663 G>A p.E555K	Hetero	DN	NA	M	23 years	NA	Gastroenteritis, Haemophilus influenzae type B meningitis, otitis, Rickettsia infection and pneumonia, bronchiectasis	No	8 / 0.6	Yes	0.33	0.06	0.21	[21]
31	AD	c.1663 G>A p.E555K	Hetero	DN	Japanese	M	25 years	6 months	Recurrent pneumonia, bronchitis, sinusitis, otitis media, mainly due to Haemophilus influenzae	Facial dysmorphic features, growth failure with GHD	0 / 0	Yes	0.09	0.01	0.01	This study

^a On immunoglobulin therapy, ^b The patient also has the heterozygous TNFRSF13B variant (c.310 T>C; p.C104R).

Pt., patient; Ref., reference; AR, autosomal recessive; AD, autosomal dominant; Homo, homozygosity; Hetero, heterozygosity; LOF, loss-of-function; HI, haploinsufficiency; DN, dominant-negative; M, male; F, female; NA, not available; B-ALL, B-cell acute lymphoid leukemia; EBV, Epstein‒Barr virus; IBS, irritable bowel syndrome; SLE, systemic lupus erythematosus; GHD, growth hormone deficiency