Table 1.

Novel clinical and laboratory features of CTLA4 haploinsufficiency due to cryptic splicing due to the c.457G>A variant

	CTLA4 haploinsufficiency	P1	P2	P3	P4
Mutation
CTLA4 gene mutation	Yes	c.457G>A	c.457+1G>A	c.457+1G>A	c.457+1G>A
Typical Clinical Manifestations of CTLA4 haploinsufficiency based on 165 reported cases
Enteropathy	58%	+	+	Absent	+
Splenomegaly	45%	Absent	Absent	Absent	Absent
Lymphadenopathy	38%	Absent	Absent	Absent	Absent
AIHA	38%	Absent	Absent	Absent	Absent
ITP	36%	Absent	Absent	Absent	Absent
Interstitial lung disease	34%	Absent	Absent	Absent	Absent
Brain lesions on MRI	21%	Absent	N.D.	Absent*	N.D.
Psoriasis	16%	Absent	Absent	Absent	Absent
Arthritis	15%	+	Absent	Absent	Absent
Autoimmune thyroiditis	12%	Absent	Absent	Absent	Absent
Lymphoma	7%	Absent	Absent	+	Absent
Novel Clinical Manifestations
Kaposi’s sarcoma	Not reported	+	Absent	Absent	Absent
Chronic fatigue	Not reported	+	Absent	Absent	Absent
Oligodendroglioma	Not reported	Absent	Absent	+	Absent
Typical Laboratory findings
Hypogammaglobulinemia or specific antibody deficiency	72%	Absent	+	Absent	Absent
CD4+ lymphopenia	22%	+	+	+	Absent
Decrease CD45RA+CD62L+ naïve T cells	74%	+	+	N.D.	Absent
Increased CD4+ FOXP3+ Tregs	% unknown	Absent	+	N.D.	N.D.
Decreased CTLA4 expression on stimulated Tregs	100%	+	+	N.D.	N.D.
Increased CD19hiCD21lo memory B cells	83%	+	+	Absent	Absent
NK cell lymphopenia	56%	+	Absent	+	Absent
Novel Laboratory findings
Increased CD4+ TEMRA	Not reported	+	Absent	Absent	Absent
Increased CD8+ TEMRA	Not reported	+	Absent	Absent	Absent
Increased DP TEMRA	Not reported	+	Absent	Absent	Absent
HHV8 testing of PBMCs
HHV8 ELISA	Not reported	+	N.D.	N.D.	N.D.
HHV8 ELISPOT	Not reported	+	N.D.	N.D.	N.D.
HHV8 PCR	Not reported	Negative	N.D.	N.D.	N.D.

N.D. not done

^*P3 had oligodendroglioma; yellow cells indicate the presence of known clinical or laboratory findings; green cells indicate the presence of novel clinical or laboratory findings