Department of Virology Laboratory, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Chin Med J (Engl). 2009 Dec 5;122(23):2851-5.
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.
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.
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).
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.
最近的研究报道了某些类型的噬血细胞性淋巴组织细胞增生症（HLH）中穿孔素基因（PRF1）的种系突变。然而，中国儿科 HLH 患者 PRF1 突变的患病率尚未得到广泛研究。本研究旨在探讨 PRF1 基因突变和序列变异在中国儿科 HLH 患者中的流行情况。
采用 5 对引物对 PRF1 的编码外显子和侧翼内含子序列进行聚合酶链反应（PCR）。随后对 30 例 HLH 儿科患者和 50 例对照进行 PCR 产物测序。
在 3 例患者中发现了 3 个编码区的杂合突变，导致氨基酸改变（C102F、S108N 和 T450M）。这些突变在对照组中未检测到。1 例患者 PRF1 存在复合杂合突变（S108N 和 T450M），为家族性 HLH 2 型（FHL2）的背景缺陷。1 例患者观察到同义序列变异（Q540Q），但在对照组中未观察到。在 HLH 患者和对照组中检测到编码区的 2 个 SNP（A274A、H300H），但两组之间的杂合率无差异（所有比较 P > 0.05）。
我们发现了 3 例 PRF1 杂合错义突变患者；其中 2 个突变（C102F 和 S108N）迄今为止仅在中国患者中发现。这些发现有助于评估中国儿科 HLH 患者 PRF1 突变的流行情况，并将其基因型与表型相关联。一些无家族史的患者可能患有原发性 HLH，即使超出了通常的年龄范围，也应怀疑这种疾病。
