Frontiers in Immunology (Mar 2019)
Pathogenic Gene Mutations or Variants Identified by Targeted Gene Sequencing in Adults With Hemophagocytic Lymphohistiocytosis
- Yi Miao,
- Yi Miao,
- Yi Miao,
- Hua-Yuan Zhu,
- Hua-Yuan Zhu,
- Hua-Yuan Zhu,
- Chun Qiao,
- Chun Qiao,
- Chun Qiao,
- Yi Xia,
- Yi Xia,
- Yi Xia,
- Yiling Kong,
- Yiling Kong,
- Yiling Kong,
- Yi-Xin Zou,
- Yi-Xin Zou,
- Yi-Xin Zou,
- Yu-Qing Miao,
- Yu-Qing Miao,
- Yu-Qing Miao,
- Xiao Chen,
- Xiao Chen,
- Xiao Chen,
- Lei Cao,
- Lei Cao,
- Lei Cao,
- Wei Wu,
- Wei Wu,
- Wei Wu,
- Jin-Hua Liang,
- Jin-Hua Liang,
- Jin-Hua Liang,
- Jia-Zhu Wu,
- Jia-Zhu Wu,
- Jia-Zhu Wu,
- Li Wang,
- Li Wang,
- Li Wang,
- Lei Fan,
- Lei Fan,
- Lei Fan,
- Wei Xu,
- Wei Xu,
- Wei Xu,
- Jian-Yong Li,
- Jian-Yong Li,
- Jian-Yong Li
Affiliations
- Yi Miao
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Yi Miao
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Yi Miao
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Hua-Yuan Zhu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Hua-Yuan Zhu
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Hua-Yuan Zhu
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Chun Qiao
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Chun Qiao
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Chun Qiao
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Yi Xia
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Yi Xia
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Yi Xia
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Yiling Kong
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Yiling Kong
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Yiling Kong
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Yi-Xin Zou
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Yi-Xin Zou
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Yi-Xin Zou
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Yu-Qing Miao
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Yu-Qing Miao
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Yu-Qing Miao
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Xiao Chen
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Xiao Chen
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Xiao Chen
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Lei Cao
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Lei Cao
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Lei Cao
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Wei Wu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Wei Wu
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Wei Wu
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Jin-Hua Liang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Jin-Hua Liang
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Jin-Hua Liang
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Jia-Zhu Wu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Jia-Zhu Wu
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Jia-Zhu Wu
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Li Wang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Li Wang
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Li Wang
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Lei Fan
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Lei Fan
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Lei Fan
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Wei Xu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Wei Xu
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Wei Xu
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- Jian-Yong Li
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
- Jian-Yong Li
- Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China
- Jian-Yong Li
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
- DOI
- https://doi.org/10.3389/fimmu.2019.00395
- Journal volume & issue
-
Vol. 10
Abstract
Hemophagocytic lymphohistiocytosis (HLH) can be classified into primary HLH and secondary HLH. Primary HLH usually occurs in infants and children with an underlying genetic defect, and there are also teens and occasional adults with primary HLH. Most cases with secondary HLH are adult patients with secondary triggers including infections, malignancies, and autoimmune diseases. The distinction between primary HLH and secondary HLH seems to be less straightforward, as patients with secondary HLH may also have genetic defects while primary HLH can be triggered by secondary causes. In this study, using amplicon-based targeted gene sequencing (TGS), we sequenced eighteen HLH-related genes in 112 adult HLH cases, which were mostly secondary HLH. Mutations or rare variants were identified in 48 cases (42.9%). All the variants except one were missense variants, and biallelic gene mutations were identified in 3 cases in which only one case harbored homogenous missense mutation. Recurrent variants including UNC13D p.G863D and AP3B1 p.T359A are much more prevalent in our cohort than in normal East Asian population, and in silico analysis predicted pathogenicity of these variants. In conclusion, according to our study, genetic defects may also contribute to the development of adult HLH cases or secondary HLH cases.
Keywords
