Objectives To detect gene mutation associated with hemophagocytic lymphohistiocytosis (HLH) and to identify mutation spectrum and clinical feature in HLH in children. Methods Thirty-seven (37) pediatric patients diagnosed with HLH according to 2004 clinical and laboratory criteria were enrolled from July 2012 to November 2015. Nucleotide sequences of all exons and their flanking intronic sequences of ten genes associated with HLH were amplified with PCR followed by direct sequencing. Point mutation analysis was performed after the direct sequencing. Results The median age of all the 37 patients was 2.6 years. The median ages of patients with gene mutation (n=22) and without gene mutation (n=15) was 2.09 years and 2.67 years, without statistical significance. Twenty-two patients were identified with gene mutations. All of them were heterozygous. UNC13D mutation (50%) is of the highest frequency in the above genes. The splicing mutations (38%) were the main type of UNC13D mutations,and missense mutations or frame-shift mutations were also found. There was no statistical difference in ages of onset and laboratory data of neutrophils, thrombocytes, NK cell activities within the three groups: multi-site mutations, single-site mutations and no mutations. EBV infection was detected in 70.3% patients. In mutation group, one patient died when he was in the period of inducing remission, and four patients were relapsed. Among them four patients were infected with EBV and one patients was negative at the onset while positive in recurrence. Conclusions UNC13D was the predominant causative gene in the Chinese population according our data. There was no significant relevance between age of onset, severity of disease and gene mutations. Attention should be paid to a patient with HLH gene mutation infected by EBV, which it might mean a poor prognosis.%目的 研究SH2D1A、XIAP、PRF1、UNC13D、STX11、STXBP2、RAB27A、AP3B1、LYST及ITK等10种儿童噬血细胞综合征(HLH)相关突变基因在HLH分布情况及相关临床特点.方法 收集2012年7月-2015年11月期间按照国际组织细胞协会HLH-2004标准确诊为HLH的37例患儿的血液样本并行基因测序,对测序结果 进行突变位点分析.结果 37名HLH患儿的中位年龄为2.6岁,检出基因突变组(22例)与未检出基因突变组(15例)中位年龄分别为2.09岁、2.67岁,差异无统计学意义(P>0.05).22例患儿检测出基因突变,均为杂合突变未见纯合突变.UNC13D突变例数最多(50%)以内含子剪切位点突变为主(38%),同时存在错义突变和移码突变.多位点突变与单一位点突变、无突变组在发病年龄、粒细胞及血小板减少程度、NK细胞数量上无明显差异.70.3%HLH患儿同时合并有EB病毒感染.4例复发、1例初诊时死亡患儿均来源于基因突变组,其中4例存在EB病毒感染,1例疾病初期无EB病毒感染,而复发时检测出EB病毒阳性.结论 UNC13D突变在中国人群的HLH较多,基因突变与患儿年龄、病情严重程度无明显相关性.
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