Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes

Journal name:
Genetics in Medicine
Published online



Precise genetic diagnosis of inherited bone marrow failure syndromes (IBMFS), a heterogeneous group of genetic disorders, is challenging but essential for precise clinical decision making.


We analyzed 121 IBMFS patients using a targeted sequencing covering 184 associated genes and 250 IBMFS patients using whole-exome sequencing (WES).


We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES. In the majority of cases (targeted sequencing: 45/53, 85%; WES: 63/68, 93%), the detected variants were concordant with, and therefore supported, the clinical diagnoses. However, in the remaining 13 cases (8 patients by target sequencing and 5 patients by WES), the clinical diagnoses were incompatible with the detected variants.


Our approach utilizing targeted sequencing and WES achieved satisfactory diagnostic rates and supported the efficacy of massive parallel sequencing as a diagnostic tool for IBMFS.

Genet Med advance online publication 19 January 2017


Fanconi anemia; inherited bone marrow failure; next-generation sequencing; target sequencing; whole-exome sequencing


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Author information

  1. The first three authors contributed equally to this work.

    • Hideki Muramatsu,
    • Yusuke Okuno &
    • Kenichi Yoshida


  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    • Hideki Muramatsu,
    • Yusuke Okuno,
    • Sayoko Doisaki,
    • Atsushi Narita,
    • Hirotoshi Sakaguchi,
    • Nozomu Kawashima,
    • Xinan Wang,
    • Yinyan Xu,
    • Asahito Hama,
    • Yoshiyuki Takahashi &
    • Seiji Kojima
  2. Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    • Kenichi Yoshida,
    • Masashi Sanada &
    • Seishi Ogawa
  3. Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    • Yuichi Shiraishi,
    • Kenichi Chiba,
    • Hiroko Tanaka &
    • Satoru Miyano
  4. Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    • Masashi Sanada &
    • Shinji Kunishima
  5. Department of Transfusion Medicine and Cell Processing, Tokyo Women’s Medical University, Tokyo, Japan

    • Hitoshi Kanno
  6. Department of Hematology, Nippon Medical School, Tokyo, Japan

    • Hiroki Yamaguchi
  7. Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan

    • Shouichi Ohga
  8. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    • Atsushi Manabe
  9. Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai, Japan

    • Hideo Harigae
  10. Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan

    • Eiichi Ishii
  11. Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan

    • Masao Kobayashi
  12. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

    • Kenichi Koike
  13. Department of Hematology/Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    • Kenichiro Watanabe
  14. Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    • Etsuro Ito
  15. Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan

    • Minoru Takata
  16. Department of Cell Transplantation and Regenerative Medicine, Tokai University Hospital, Isehara, Japan

    • Miharu Yabe
  17. Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    • Satoru Miyano

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