Pathogenic Gene Mutations or Variants Identified by Targeted Gene Sequencing in Adults With Hemophagocytic Lymphohistiocytosis

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...

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Published inFrontiers in immunology Vol. 10; p. 395
Main Authors Miao, Yi, Zhu, Hua-Yuan, Qiao, Chun, Xia, Yi, Kong, Yiling, Zou, Yi-Xin, Miao, Yu-Qing, Chen, Xiao, Cao, Lei, Wu, Wei, Liang, Jin-Hua, Wu, Jia-Zhu, Wang, Li, Fan, Lei, Xu, Wei, Li, Jian-Yong
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 07.03.2019
Subjects
AP3B1
hemophagocytic lymphohistiocytosis
Immunology
ITK
mutation
targeted gene sequencing
UNC13D
ITK
mutation
targeted gene sequencing
PRF1
hemophagocytic lymphohistiocytosis
AP3B1
LYST
UNC13D
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Summary: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 p.G863D and p.T359A are much more prevalent in our cohort than in normal East Asian population, and 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.
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Reviewed by: Grant Schulert, Cincinnati Children's Hospital Medical Center, United States; Kimberly Gilmour, Great Ormond Street Hospital for Children NHS Foundation Trust, United Kingdom
Edited by: Guzide Aksu, Ege University, Turkey
This article was submitted to Primary Immunodeficiencies, a section of the journal Frontiers in Immunology
These authors have contributed equally to this work
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.00395