title: Mutations in the perforin gene in children with hemophagocytic lymphohistiocytosis.
abstract: BACKGROUND
  Recent studies have reported germline mutations in the perforin gene (PRF1) in some types of hemophagocytic lymphohistiocytosis (HLH). However, the prevalence of PRF1 mutations in HLH in Chinese pediatric patients has not been extensively studied. The aim of this study was to investigate the prevalence of mutations and sequence variations in the PRF1 gene in Chinese pediatric patients with HLH.
  
  
  METHODS
  Polymerase chain reaction (PCR) was performed with five pairs of primers for the coding exons and the flanking intron sequences of PRF1. Sequencing of PCR products was subsequently applied in 30 pediatric patients with HLH and in 50 controls.
  
  
  RESULTS
  Three heterozygous mutations in a coding region were found, which resulted in amino acid changes (C102F, S108N and T450M) in three patients. These mutations were not detected in control subjects. One patient had compound heterozygous mutations (S108N and T450M) in PRF1 as the background defect, and documented familial HLH type 2 (FHL2). One synonymous sequence variant (Q540Q) was observed in one patient but not in the controls. Two SNPs (A274A, H300H) in the coding region were detected in HLH patients and controls, but without differences in the heterozygosity rate between the two groups (P > 0.05 for all comparisons).
  
  
  CONCLUSIONS
  We have identified three patients with three heterozygous missense mutations in PRF1; two of those three mutations (C102F and S108N) have so far been found only from Chinese patients. These findings are useful in evaluating the prevalence of PRF1 mutations in Chinese pediatric patients with HLH, and to correlate their genotype with phenotype. Some patients without familial history probably have primary HLH, which should be suspected even beyond the usual age range.
authors.affiliation: Department of Virology Laboratory, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Lu
authors.forename: Zheng-de
authors.initials: ZD
authors.lastname: Xie
authors.forename: Kun-ling
authors.initials: KL
authors.lastname: Shen
authors.forename: Ling-jun
authors.initials: LJ
authors.lastname: Ye
authors.forename: Run-hui
authors.initials: RH
authors.lastname: Wu
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Liu
authors.forename: Ying-kang
authors.initials: YK
authors.lastname: Jin
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*
chemical_list: C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin