Table 1. Molecular features of somatic... | Rockefeller University Press

Table 1.

Molecular features of somatic reversion and EBV infection in XLP patients

XLP patient	Age at analysis	Clinical features	Current status	Original mutation	Reversion	Reversion mutation	% SAP⁺ cells in PBMCs	EBV status
	yr						%
1	36–47	•Clinical EBV: severe (19 yr)	•Deceased (age 49 yr)	c.161A>G; Y54C	Yes	c.161G>A; C54Y	4.42	+
		•HLH: yes (49 yr)	•Deceased (age 49 yr)	c.161A>G; Y54C
		•Lymphoma: B-cell lymphoma, large bowel (10 yr)
		•Hypogamma: yes (19 yr)
		•Other: meningitis (19 yr), lymphoproliferation of CD4⁺CD8⁺ T cells (40 yr)
2	38–45	•Clinical EBV: mild (17 yr)	•Stable	c.259T>C; F87S	Yes	c.259C>T/A; S87Y; S87F	8.45	+
		•HLH: nil	•On IVIg	c.259T>C; F87S		c.259C>T/A; S87Y; S87F
		•Lymphoma: nil
		•Hypogamma: yes (26 yr)
3	42–52	•Clinical EBV: mild (20 yr)	•Stable	c.259T>C; F87S	Yes	c.259C>A; S87Y	2.29	+
		•HLH: nil	•On IVIg	c.259T>C; F87S
		•Lymphoma: nil
		•Hypogamma: yes (21 yr)
5	11–17	•Clinical EBV: nil	•Stable	c.251T>C; I84T	Yes	c.251C>T; T84I	1.67	+
		•HLH: nil
		•Lymphoma: B-cell lymphoma
		•Hypogamma: nil
8	16	•Clinical EBV: severe (10-12 yr); severe reactivation (21 yr)	•BMT (age 21 yr)	c.251T>C; I84T	Yes	c.251C>T; T84I	1.63	+
		•HLH: nil	•Stable
		•Lymphoma: nil
		•Hypogamma: yes (13 yr)
10	31	•Clinical EBV: nil	•Deceased (age 31 yr)	c.163C>T; R55X	Yes	c.163T>A/C; X55R	1.82	+
		•HLH: yes (26 yr)	•Deceased (age 31 yr)	c.163C>T; R55X		c.163T>A/C; X55R
		•Lymphoma: nil
		•Hypogamma: nil
		•Other: vasculitis
11	34	•Clinical EBV: fulminant	•Stable	Deletion	No	NA	Nil	+
		•HLH: nil	•On IVIg
		•Lymphoma: nil
		•Hypogamma: nil
		•Other: psoriasis, chronic active hepatitis, IBD
23	38	•Clinical EBV: severe (12 yr)	•Deceased (age 37 yr)	ND	Yes	ND	1.94	+
		•HLH: nil	•Deceased (age 37 yr)
		•Lymphoma: unknown
		•Hypogamma: yes (16 yr)
24	3	•Clinical EBV: fulminant (3 yr)	•Stable 3 yr after BMT	c.3G>T; M1I	No	NA	<LOD	+ (acute infection)
		•HLH: yes (3 yr)	•Stable 3 yr after BMT					+ (acute infection)
		•Lymphoma: possible non-Hodgkin’s lymphoma (3 yr)
		•Hypogamma: unknown
25	17	•Clinical EBV: nil	•Stable 2 yr after BMT	c.3G>T; M1I	No	NA	<LOD	−
		•HLH: nil	•Stable 2 yr after BMT
		•Lymphoma: small bowel lymphoma (12 yr)
		•Hypogamma: yes
26	11	•Clinical EBV: nil	•Stable	c.160T>C; Y54H	Yes	Below limit of sensitivity	0.01	+
		•HLH: nil	•On IVIg	c.160T>C; Y54H		Below limit of sensitivity
		•Lymphoma: nil
		•Hypogamma: yes (7 yr)
27	Cord blood	•Clinical EBV: nil	•Deceased	c.163C>T; R55X	No	NA	<LOD	−
		•HLH: nil		c.163C>T; R55X
		•Lymphoma: nil
		•Hypogamma: nil

XLP patient	Age at analysis	Clinical features	Current status	Original mutation	Reversion	Reversion mutation	% SAP⁺ cells in PBMCs	EBV status
	yr						%
1	36–47	•Clinical EBV: severe (19 yr)	•Deceased (age 49 yr)	c.161A>G; Y54C	Yes	c.161G>A; C54Y	4.42	+
		•HLH: yes (49 yr)	•Deceased (age 49 yr)	c.161A>G; Y54C
		•Lymphoma: B-cell lymphoma, large bowel (10 yr)
		•Hypogamma: yes (19 yr)
		•Other: meningitis (19 yr), lymphoproliferation of CD4⁺CD8⁺ T cells (40 yr)
2	38–45	•Clinical EBV: mild (17 yr)	•Stable	c.259T>C; F87S	Yes	c.259C>T/A; S87Y; S87F	8.45	+
		•HLH: nil	•On IVIg	c.259T>C; F87S		c.259C>T/A; S87Y; S87F
		•Lymphoma: nil
		•Hypogamma: yes (26 yr)
3	42–52	•Clinical EBV: mild (20 yr)	•Stable	c.259T>C; F87S	Yes	c.259C>A; S87Y	2.29	+
		•HLH: nil	•On IVIg	c.259T>C; F87S
		•Lymphoma: nil
		•Hypogamma: yes (21 yr)
5	11–17	•Clinical EBV: nil	•Stable	c.251T>C; I84T	Yes	c.251C>T; T84I	1.67	+
		•HLH: nil
		•Lymphoma: B-cell lymphoma
		•Hypogamma: nil
8	16	•Clinical EBV: severe (10-12 yr); severe reactivation (21 yr)	•BMT (age 21 yr)	c.251T>C; I84T	Yes	c.251C>T; T84I	1.63	+
		•HLH: nil	•Stable
		•Lymphoma: nil
		•Hypogamma: yes (13 yr)
10	31	•Clinical EBV: nil	•Deceased (age 31 yr)	c.163C>T; R55X	Yes	c.163T>A/C; X55R	1.82	+
		•HLH: yes (26 yr)	•Deceased (age 31 yr)	c.163C>T; R55X		c.163T>A/C; X55R
		•Lymphoma: nil
		•Hypogamma: nil
		•Other: vasculitis
11	34	•Clinical EBV: fulminant	•Stable	Deletion	No	NA	Nil	+
		•HLH: nil	•On IVIg
		•Lymphoma: nil
		•Hypogamma: nil
		•Other: psoriasis, chronic active hepatitis, IBD
23	38	•Clinical EBV: severe (12 yr)	•Deceased (age 37 yr)	ND	Yes	ND	1.94	+
		•HLH: nil	•Deceased (age 37 yr)
		•Lymphoma: unknown
		•Hypogamma: yes (16 yr)
24	3	•Clinical EBV: fulminant (3 yr)	•Stable 3 yr after BMT	c.3G>T; M1I	No	NA	<LOD	+ (acute infection)
		•HLH: yes (3 yr)	•Stable 3 yr after BMT					+ (acute infection)
		•Lymphoma: possible non-Hodgkin’s lymphoma (3 yr)
		•Hypogamma: unknown
25	17	•Clinical EBV: nil	•Stable 2 yr after BMT	c.3G>T; M1I	No	NA	<LOD	−
		•HLH: nil	•Stable 2 yr after BMT
		•Lymphoma: small bowel lymphoma (12 yr)
		•Hypogamma: yes
26	11	•Clinical EBV: nil	•Stable	c.160T>C; Y54H	Yes	Below limit of sensitivity	0.01	+
		•HLH: nil	•On IVIg	c.160T>C; Y54H		Below limit of sensitivity
		•Lymphoma: nil
		•Hypogamma: yes (7 yr)
27	Cord blood	•Clinical EBV: nil	•Deceased	c.163C>T; R55X	No	NA	<LOD	−
		•HLH: nil		c.163C>T; R55X
		•Lymphoma: nil
		•Hypogamma: nil

BMT, BM transplant; HLH, hemophagocytic lymphohistiocytosis; hypogamma, hypogammaglobulinemia; IVIg, intravenous Ig; LOD, limit of detection by flow cytometry; NA, not applicable. XLP2 and XLP3 are siblings; XLP5 and XLP8 are first cousins. The values in parentheses indicate age of presentation of each clinical feature. EBV load was determined by quantitative PCR.

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