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Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis
Author(s) -
Zhizhuo Huang,
Junmei Xu,
Yuelin Shen,
Qiang Qin,
Chunyan Liu,
Zhengde Xie,
Kunling Shen
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.23216
Subject(s) - compound heterozygosity , xiap , missense mutation , medicine , exon , mutation , genetics , gene , biology , apoptosis , programmed cell death , caspase
Background This study aimed to investigate the prevalence of mutations in the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK in Chinese pediatric patients with EBV‐HLH. Methods Sixty‐seven pediatric patients diagnosed with EBV‐HLH in Beijing Children's Hospital were recruited. Nucleotide sequences of all exons and their flanking intronic sequences of PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK were amplified by PCR followed by direct sequencing. Results Eight patients were identified with heterozygous, compound heterozygous, or homozygous mutations in PFR1, UNC13D, and XIAP. Three missense mutations (c.83G>A, c.503G>A, c.632C>T) were found in PRF1 of two males and two females. Compound heterozygous c.93C>G and c.1066C>T were found in PRF1 of a 2.5‐year‐old female. Four different mutations were found in UNC13D of two patients: compound nonsense heterozygous mutations c.766C>T and c.1215C>G were found in one male and two splicing mutations c.1596+1G>C and c.2709+1G>A were found in another male. A heterozygous mutation c.1099+2T>C in XIAP was found in a 4‐year‐old male. No detrimental mutations were identified in STX11, SH2D1A, or ITK. NK cell activity did not differ between the eight FHL patients and the remaining patients. There was no statistical difference in clinical features and laboratory data for these two subgroups with biallelic and heterozygous mutations. Conclusions Seven novel mutations in PRF1, UNC13D, and XIAP were identified in EBV‐HLH patients. Only a fraction of the Chinese children with EBV‐HLH have genetic defects in PRF1, UNC13D, and XIAP. There were no gene mutations of PRF1/UNC13D/STX11/SH2D1A/XIAP/ITK in the majority of Chinese child patients with EBV‐HLH. Pediatr Blood Cancer 2012; 58: 410–414. © 2011 Wiley Periodicals, Inc.