Abstract:Objective To investigate the prevalence of mutations and sequence variations in X-linked inhibitor of apoptosis (XIAP) gene among Chinese pediatric patients with hemophagocytic lymphohistiocytosis (HLH). Methods Sixty-five children who were diagnosed with HLH between January 2009 and December 2012 (case group), as well as 70 healthy children (control group), were enrolled in the study. The exons of XIAP gene (1-1, 1-2, 2-6) were amplified by PCR and directly sequenced. The genotypic and allelic frequencies of single nucleotide polymorphism (SNP) were analyzed. Results None of the HLH patients showed mutations in these exons of XIAP gene. Only one nonsynonymous SNP, rs5956583 located in exon 5, was observed, but there were no significant differences in the genotypic and allelic frequencies of this SNP between the case and control groups (P>0.05). Conclusions HLH caused by XIAP mutations may be rare in children. SNP rs5956583 of XIAP gene may have little contribution to the development of childhood HLH.
Filipovich AH. Hemophagocytic lymphohistiocytosis and related disorders[J]. Curr Opin Allergy Clin Immunol, 2006, 6(6):410-415.
[3]
Henter JI, Horne AC, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis[J]. Pediatr Blood Cancer, 2007, 48(2): 124-131.
[4]
Rigaud S, Fondaneche MC, Lambert N, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome[J]. Nature, 2006, 444(7115): 110-114.
Lewis J, Burstein E, Reffey SB, et al. Uncoupling of the signaling and caspase-inhibitory properties of X-linked inhibitor of apoptosis[J]. J Biol Chem, 2004, 279(10): 9023-9029.
[7]
Birkey Reffey S, Wurthner JU, Parks WT, et al. X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling[J]. J Biol Chem, 2001, 276(28): 26542-26549.
[8]
Hofer-Warbinek R, Schmid JA, Stehlik C, et al. Activation of NF-kappa B by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1[J]. J Biol Chem, 2000, 275(29): 22064-22068.
[9]
Krieg A, Correa RG, Garrison JB, et al. XIAP mediates NOD signaling via interaction with RIP2[J]. Proc Natl Acad Sci U S A, 2009, 106(34): 14524-14529.
Marsh RA, Madden L, Kitchen BJ, et al. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease[J]. Blood, 2010, 116(7): 1079-1082.
[12]
Filipovich AH, Zhang K, Snow AL, et al. X-linked lymphoproliferative syndromes: brothers or distant cousins?[J]. Blood, 2010, 116(18): 3398-3408.
[13]
Molleran Lee S, Villanueva J, Sumegi J, et al. Characterization of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis[J]. J Med Genet, 2004, 41(2): 137-144.
[14]
Zur Stadt U, Schmidt S, Kasper B, et al. Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11[J]. Hum Mol Genet, 2005, 14(6): 827-834.
Ferretti M, Gattorno M, Chiocchetti A, et al. The 423Q polymorphism of the X-linked inhibitor of apoptosis gene influences monocyte function and is associated with periodic fever[J]. Arthritis & Rheumatism, 2009, 60(11): 3476-3484.