TABLE 2.

The EBV‐DNA load and genetic characteristics of 10 late‐onset primary HLH cases and their families

Case number	Relationship	Age (y)	EBV (copies/μg)	Gene	Protein	1000 genome	SIFT (<0.05)
Case 1	Proband	14	(1.2 $\pm$0.1) × 107	AP3B1	S671F	–	0.049 (Damaging)
	Father	40	<5 × 102	Normal	–
	Mother	39	<5 × 102	AP3B1	S671F
	Brother	0.75	<5 × 102	AP3B1	S671F
Case 2	Proband	18	(3.3 $\pm$0.5) × 107	LYST	H151R	–	0.042 (Damaging)
				UNC13D	S919F	–	0.699 (Tolerated)
	Father	50	<5 × 102	LYST	H151R
	Mother	49	<5 × 102	UNC13D	S919F
Case 3	Proband	25	(5.4 $\pm$ 1.5) × 105	PRF1	G306S	–	0.010 (Damaging)
				PRF1	P22RfsX29	–	–
	Father	48	(4.1 $\pm$1.1) × 103	PRF1	P22RfsX29
	Mother	47	<5 × 102	PRF1	G306S
	Brother	23	<5 × 102	PRF1	G306S
				PRF1	P22RfsX29
	Son	1	(3.2 $\pm$0.8) × 103	PRF1	G306S
Case 4	Proband	45	(1.9$\pm$0.3) × 107	STX11	R49Q	0.02	1.000 (Tolerated)
				PRF1	R225Q	–	0.366 (Tolerated)
	Father	70	<5 × 102	STX11	R49Q
	Mother	69	<5 × 102	PRF1	R225Q
	Brother	47	<5 × 102	STX11	R49Q
	Brother	43	<5 × 102	PRF1	R225Q
	Sister	40	<5 × 102	PRF1	R225Q
	Son	16	<5 × 102	PRF1	R225Q
	Daughter	18	<5 × 102	STX11(hom)	R49Q
	Husband	48	<5 × 102	STX11	R49Q
Case 5	Proband	12	(1.3 $\pm$0.4) × 107	ITK	R581W	0.001	0.007 (Damaging)
	Father	39	<5 × 102	Normal
	Mother	37	<5 × 102	ITK	R581W
Case 6	Proband	25	(7.7 $\pm$1.9) × 105	STXBP2	R566G	0.012	0.035 (Damaging)
	Father	50	<5 × 102	Normal
	Mother	49	<5 × 102	STXBP2	R566G
	Elder Sister	27	<5 × 102	STXBP2	R566G
	Younger Sister	23	<5 × 102	Normal
Case 7	Proband	21	(1.3$\pm$0.7) × 107	UNC13D UNC13D	G863D A397T	0.001 ‐	0.000 (Damaging) 0.262 (Tolerated)
	Father	45	<5 × 102	UNC13D	G863D
	Mother	44	<5 × 102	UNC13D	A397T
Case 8	Proband	18	(6.5$\pm$1.3) × 107	UNC13D UNC13D	G863D I410L	0.001 0.003	0.000 (Damaging) 1.000 (Tolerated)
	Father	43	<5 × 102	UNC13D UNC13D	G863D I410L
	Mother	42	<5 × 102	Normal
Case 9	Proband	32	(4.0 $\pm$ 1.1) × 106	GZMB	R120W	–	0.031 (Damaging)
	Father	54	(1.2 $\pm$0.3) × 103	GZMB	R120W
	Mother	53	<5 × 102	Normal	–
	Sister	35	<5 × 102	GZMB	R120W
Case 10	Proband	13	(1.2$\pm$0.4) × 107	RAB27A	R187Q	0.009	0.372 (Tolerated)
	Father	38	<5 × 102	RAB27A	R187Q
	Mother	36	(1.2$\pm$0.6) × 104	Normal	–
	Brother	8	<5× 102	Normal	–

1000 genome, also known as 1000 genome project, is a map of human genome variation from population‐scale sequencing, the number stands for the frequency of amino acid substitution in the database. "‐" means amino acid substitution can't be detected in the database. SIFT predicts whether an amino acid substitution affects protein function. The lower the score, the more likely to be harmful.

Abbreviations: hom, homozygote; y, year.