Gene mutation associated with hemophagocytic lymphohistiocytosis in children / 临床儿科杂志

ABSTRACT

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.