International Journal of Hematology

, Volume 106, Issue 2, pp 282–290 | Cite as

Exome sequencing for simultaneous mutation screening in children with hemophagocytic lymphohistiocytosis

  • Ekchol Mukda
  • Objoon Trachoo
  • Ekawat Pasomsub
  • Rawiphorn Tiyasirichokchai
  • Nareenart Iemwimangsa
  • Darintr Sosothikul
  • Wasun Chantratita
  • Samart PakakasamaEmail author
Original Article


In the present study, we used exome sequencing to analyze PRF1, UNC13D, STX11, and STXBP2, as well as genes associated with primary immunodeficiency disease (RAB27A, LYST, AP3B1, SH2D1A, ITK, CD27, XIAP, and MAGT1) in Thai children with hemophagocytic lymphohistiocytosis (HLH). We performed mutation analysis of HLH-associated genes in 25 Thai children using an exome sequencing method. Genetic variations found within these target genes were compared to exome sequencing data from 133 healthy individuals. Variants identified with minor allele frequencies <5% and novel mutations were confirmed using Sanger sequencing. Exome sequencing data revealed 101 non-synonymous single nucleotide polymorphisms (SNPs) in all subjects. These SNPs were classified as pathogenic (n = 1), likely pathogenic (n = 16), variant of unknown significance (n = 12), or benign variant (n = 72). Homozygous, compound heterozygous, and double-gene heterozygous variants, involving mutations in PRF1 (n = 3), UNC13D (n = 2), STXBP2 (n = 3), LYST (n = 3), XIAP (n = 2), AP3B1 (n = 1), RAB27A (n = 1), and MAGT1 (n = 1), were demonstrated in 12 patients. Novel mutations were found in most patients in this study. In conclusion, exome sequencing demonstrated the ability to identify rare genetic variants in HLH patients. This method is useful in the detection of mutations in multi-gene associated diseases.


Exome sequencing Hemophagocytic lymphohistiocytosis Next-generation sequencing Molecular diagnosis Mutation screening 



The authors thank Patcharee Komvilaisak, M.D. for referring patients for genetic evaluation. This study was supported by the Katawethi Fund. EM was supported by a PhD student scholarship award from Thammasat University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Ekchol Mukda
    • 1
    • 2
  • Objoon Trachoo
    • 3
  • Ekawat Pasomsub
    • 4
  • Rawiphorn Tiyasirichokchai
    • 2
  • Nareenart Iemwimangsa
    • 4
  • Darintr Sosothikul
    • 5
  • Wasun Chantratita
    • 4
  • Samart Pakakasama
    • 2
    Email author return OK on get
  1. 1.Molecular Medicine Program, Multidisciplinary Unit, Faculty of ScienceMahidol UniversityBangkokThailand
  2. 2.Department of Pediatrics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
  3. 3.Department of Medicine, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
  4. 4.Department of Pathology, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
  5. 5.Department of Pediatrics, Faculty of MedicineChulalongkorn UniversityBangkokThailand

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