So far, heterozygous pathogenic variants have been documented in seventeen genes (PTPN11, SOS1, SOS2, KRAS, NRAS, RAF1, SHOC2, CBL, RRAS, RIT1, RASA2, MAP3K8
, SPRY1, MYST4, LZTR1, A2ML1, and PP1CB) that underlie this disorder or clinically related phenotypes [1, 2].
These genes encoded cytokines (CSF3, CSF2, CCL3, TNF, CCR1, IL13, KIT, CCL5, CCL4, IL10, CXCL10, IL12RB2, IFNG, IL1B, IL1A, IL8, MET, CD40, HGF, LEP, CXCL16, CX3CR1, CCR2, PDGFRA, IL12B, IL2), lipid metabolism related genes (CD36, GPX4, LPIN1, LPL, LPB), transcription regulators (BCL3, FOS and NFKBIA), receptors (TNF, IL8, RELA, TLR1, TIRAP, TLR2, NFKBIA, NFKB1, TLR4, CD40, CCL5, CXCL10, FOS, JUN, MAP3K8
, IL1B, LBP, IL12B, CD14, SPP1), and others such as SELP, SELL, and SOD1, all play a role in some aspect of the immune response including cytokine activity (IL10, TNF, IL8, and IL1B), cell adhesion (SELL and SELP), immune activation (CD14 and TLR2), acute phase reaction (TNF, IL1B, and SAA3), apoptosis (BCL2, BAX).
GPX3, TLR2, BDKRB1, FBXO5, BRCA1, MAP3K8
, SCARB1, and 6 lncRNAs (XR_111050, NR_024031, FR374455, FR401275, FR406817, and FR148647) played a key role in osteogenic process, and lncRNA XR_111050 promoted osteogenic differentiation of mesenchymal stromal cells .