Screening and clinical research into PRF1 gene mutations in children with hemophagocytic syndrome.

LU Gen; SHEN Kun-ling; XIE Zheng-de; WU Run-hui; YANG Shuang; LIU Chun-yan

Abstract：Objective To investigate the prevalence of mutations and sequence variations of PRF1 gene in Chinese pediatric patients with hemophagocytic syndrome(HPS)and to explore the possible relationship between gene mutations and clinical manifestations.Methods Polymerase chain reaction(PCR) was performed on five pairs of primem for the ceding exons and the flanking intron sequences of the PRF1 gene.PCR products sequencing wag subsequently applied to 30 pediatric patients with HLH and 50 controls.Results Three heterozygous mutations in coding region were found,which resulted in amino acid change(C102F,S108N and T450M)in 3 patients.Those mutations were not detected in control subjects.One patient has compound heterozygous mutations(S108N and T450M)in the PRF1 gene,which was clearly diagnosed as familial HLH type 2(FHL2).One synonymous sequence variant(QS40Q) was observed in one patient but not in the controls.Two SNPs(A274A,H300H)in coding region beth in HLH patients and controls were detected,but the heterozygosity rate had no difference between the two groups.Conclusion PRF1 gene mutations exist in Chinese children with HLH,and the mutation loci of C102F and S108N only exist in Chinese children,which shows that the PRF1 gene mutations in HLH children in China have their own characteristics.The HLH children without familial HLH history or with late onset may have familial HLH.