title: [The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistiocytosis].
abstract: OBJECTIVE
  To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes.
  
  
  METHODS
  From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up.
  
  
  RESULTS
  Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11, XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH (EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH), 1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t(15;17) (q22;q25) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV.
  
  
  CONCLUSIONS
  Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH, some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.
authors: Beijing Daopei Hospital, Beijing 100049, China. tongcr.21@163.com
authors: Chun-Rong
authors: CR
authors: Tong
authors: Hong-Xing
authors: HX
authors: Liu
authors: Jian-Jun
authors: JJ
authors: Xie
authors: Fang
authors: F
authors: Wang
authors: Peng
authors: P
authors: Cai
authors: Hui
authors: H
authors: Wang
authors: Juan
authors: J
authors: Zhu
authors: Wen
authors: W
authors: Teng
authors: Xian
authors: X
authors: Zhang
authors: Jun-Fang
authors: JF
authors: Yang
authors: Ya-Li
authors: YL
authors: Zhang
authors: Xin-Hong
authors: XH
authors: Fei
authors: Jie
authors: J
authors: Zhao
authors: Yu-Ming
authors: YM
authors: Yin
authors: Tong
authors: T
authors: Wu
authors: Jing-Bo
authors: JB
authors: Wang
authors: Yuan
authors: Y
authors: Sun
authors: Rong
authors: R
authors: Liu
authors: Xiao-Dong
authors: XD
authors: Shi
authors: Dao-Pei
authors: DP
authors: Lu