Deciphering Kawasaki disease genetics through next-generation sequencing: A scoping review

Table 1 Summary of genes identified in Kawasaki disease through whole exome sequencing, whole genome sequencing, and targeted sequencing approaches

Ref.	Cohort size	Sequencing approach	Genetic variants identified	rs IDs (reference SNP IDs)	Observed associations
Kim et al[23]	6 family members including 2 siblings affected with KD (n = 6)	WGS	Rare: TLR6, MEF2A common: ARRDC4, SLK, TACSTD2	rs5743809, rs35220466, rs12650224, rs6822503, rs12645200, rs5743826, rs6837101, rs373652230, rs1552673, rs10786779, rs6584583 and rs14008	TLR6-NF-κB signalling pathway upregulation
Kanda et al[42]	Refractory KD (n = 1)	WGS	ORAI1, BLK	rs3741596 and rs2254546	Calcineurin/NFAT signalling pathway upregulation
Shrestha et al[34]	KD (n = 472)	WGS	FANK1, MAP2K3, KCNJ12, FRG1DP, FRG1BP, DEFB115, CWH43, CCZ1B, MIR3683, FRG1JP, FLJ43315	rs77740910, rs73368612, rs113336767, rs75317727, C20_29079715, C20_30491365, C4_49554582, C7_6981323, C9_63906587	IVIG resistance
			CA10	rs74255119	IVIG responsiveness
Shrestha et al[35]	KD (n = 504)	WGS	KLRC2, ZMAT4, NDUFA5, MICU2, PTPRD, TCAF2, WHAMM, LOC100127, ACTR3BP2, MYBPC3, FRG1DP	rs62154092, rs28730284, rs9643846, rs9643847, rs57504215, rs60545202, rs59556769, rs73677451, rs12676292, rs4332118, rs6988966, rs10276547, rs10280266, rs600075, rs5896385, rs1218424730, rs11259953, rs11259954, rs34163760, rs12585631, rs1052373, rs1424006606, rs1396081550, rs1258107032, rs1379390981, rs1424309393	Disease susceptibility, severity, and CAAs involving immune dysregulation, mitochondrial dysfunction and vascular remodelling pathways
Kim et al[33]	KD (n = 200)	WES	FCRLA, PTGER4, IL17F, CARD11, SIGLEC10	rs2275603, rs755244149, rs117796773, rs41493047, and rs201376644	Disease susceptibility
			IL31RA, FGFR4, FNDC1, MMP8, FOXN1	rs148721785, rs201812753, rs374967242, rs61754773, and rs188424977	Development of CAAs
Zhang et al[22]	KD (n = 93)	WES	RBP3 and MYH14	RBP3: c.2650G>A, MYH14: c.566G>A, MYH14: c.1109C>T, MYH14: c.3917T>G, MYH14: c.4301G>A, MYH14: c.5026C>T, MYH14: c.5329 C>T, MYH14: c.5393 C>A, and MYH14: c.5476 C>T	Rare coding variants
Xu et al[40]	KD (n = 1272)	WES	USH2A, LMO7, CEMIP, EFCC1	rs148135241, rs142687160, rs12441101, and rs142391828	Sex-biased variants
Wang et al[44]	KD (n = 110)	WES	HLA-DRB1, IL6ST, IL17RC, VEGFB, ITPKC, CASP3, ORAI1, MYH11, SMAD9	rs17882084, rs781455079, rs143781415, rs776229557, rs76358638, rs577739464, rs769061106, rs146388001, rs185661462, rs758895653, rs767136120, rs397514715 and rs200651392	Disease susceptibility and development of CAAs
Nakamura et al[46]	KD + PFAPA (n = 3)	WES	CARD8	rs140826611	Inflammasome link (NLRP3 regulation)
Chen et al[21]	KD (n = 330)	Targeted gene panel	CD247, PPIE, FLT4, CUL1, LBP, IL2RA, MAP2K1, MAPK11	rs840016, rs2463260, rs56401579, rs56193546, rs10271133, rs2007404, rs12358961, rs16949924, rs2232595, and rs742185	IVIG resistance
			ACVR2B, CD24	rs77317995, rs6530599, rs6530600, rs1136210	IVIG responsiveness
Amano et al[38]	KD (n = 82)	Targeted gene panel	IL-4R	rs563535954	IVIG responsiveness
Song et al[39]	KD (n = 190)	Targeted gene panel	ITPR3, PIK3CD, PRKCZ	rs2229634, rs11121484, rs1141402, rs34108055	Dysregulated innate immune signaling in KD

KD: Kawasaki disease; WES: Whole exome sequencing; WGS: Whole genome sequencing; IVIG: Intravenous immunoglobulin; CAA: Coronary artery abnormalities; SNP: Single nucleotide polymorphism; rs ID: Reference SNP identifier.