title: Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
abstract: 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.
authors.affiliation: Department of Virology Laboratory, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Zhizhuo
authors.forename: Xu
authors.initials: X
authors.lastname: Junmei
authors.forename: Shen
authors.initials: S
authors.lastname: Yuelin
authors.forename: Qin
authors.initials: Q
authors.lastname: Qiang
authors.forename: Liu
authors.initials: L
authors.lastname: Chunyan
authors.forename: Xie
authors.initials: X
authors.lastname: Zhengde
authors.forename: Shen
authors.initials: S
authors.lastname: Kunling
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051359:Lymphohistiocytosis, Hemophagocytic / Q000453:epidemiology* / Q000235:genetics* / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics; D015995:Prevalence; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D050765:Qa-SNARE Proteins / Q000235:genetics; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D050765:Qa-SNARE Proteins; C114953:SH2D1A protein, human; C541732:STX11 protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C507969:UNC13D protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein; D054353:Perforin; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase