Table 3

HLH-associated genetic mutations (N=69).

Gene	Nucleotide change	Amino acid change	Mutation type	Novelty	N of Patients	Age at onset (mo), median, range	Patient status (alive/dead)	Reference
PRF1	c.673C>T	p.(Arg225Trp)	Missense	Reported	1	83.9	0/1	Stepp et al. [33]
	c.1122G>A	p.(Trp374*)	Nonsense	Reported	3	2.6 (0–6.0)	1/2	Balta et al. [24]
	c.50delT	p.(Leu17ArgfsTer34)	Frameshift	Reported	2	2.7 (2.3–3.0)	0/2	Trizzino et al. [34]
	c.1081A>T	p.(Arg361Trp)	Missense	Reported	1	11.4	0/1	Gadoury-Levesque et al. [35]
UNC13D	c.1484T>G	p.(Val495Gly)	Missense	Novel	1	72.4	1/0	This study, Supplementary Fig. 1C
	c.3047_3048insC	p.(Glu1017ArgfsTer8)	Frameshift	Novel	6	2.4 (1.9–11.6)	4/2	This study, Supplementary Fig. 1A
	c.3053C>A	p.(Ala1018Asp)	Missense	Novel	2	2.6 (1.9–3.3 )	2/0	This study, Supplementary Fig. 1D
	c.2019C>G	p.(Tyr673*)	Nonsense	Novel	1	15.1	1/0	This study, Supplementary Fig. 1B
	c.766C>T	p.(Arg256*)	Nonsense	Reported	2	1.9 (1.6–2.1)	2/0	Zur Stadt et al. [19]
STXBP2	c.862T>C	p.(Trp288Arg)	Missense	Novel	1	0.43	0/1	This study, Supplementary Fig. 2
	c.1430C>T	p.(Pro477Leu)	Missense	Reported	24	3.7 (0.8–14.2)	16/8	zur Stadt et al. [15]
	c.1034C>T	p.(Thr345Met) (monoallelic)	Missense	Novel	2	7.2 (5.3–9.0)	0/2	This study
STX11	c.601_602ins C	p.(Gln140ProfsTer46)	Frameshift	Novel	1	16.9	1/0	This study, Supplementary Fig. 3
	c.690G>A	p.(Gln230Ala) (monoallelic)	Missense	Novel	1	9.5	0/1	This study
	c.173T>C	p.(Leu58Pro)	Missense	Reported	14	12.1 (0.7–63.6)	9/5	Zur Stadt et al. [19]
LYST	c.4637C>T	p.(Ala1546Val)	Missense	Novel	1	10.9	0/1	This study, Supplementary Fig. 4C
	c.9560+1G>C	Splice site	Splice site	Novel	1	46.9	1/0	This study, Supplementary Fig. 4B
	c.9044+1G>T	Splice site	Splice site	Novel	2	59.9 (47.0–72.9)	2/0	This study, Supplementary Fig. 4A
RAB27A	c.400A>C	p.(Lys134Gln)	Missense	Novel	2	12.0 (8.0–16.0)	1/1	This study, Supplementary Fig. 5
XIAP	c.1190insA	p. (Ile397Asnfs Ter405)	Frameshift	Reported	1	39.3	0/1	Aguilar et al. [36]

Blood Res 2021;56:86~101 https://doi.org/10.5045/br.2021.2020308