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

Hideki Muramatsu¹, Yusuke Okuno¹, Kenichi Yoshida², Yuichi Shiraishi³, Sayoko Doisaki¹, Atsushi Narita¹, Hirotoshi Sakaguchi¹, Nozomu Kawashima¹, Xinan Wang¹, Yinyan Xu¹, Kenichi Chiba³, Hiroko Tanaka³, Asahito Hama¹, Masashi Sanada^{2

4}, Yoshiyuki Takahashi¹, Hitoshi Kanno⁵, Hiroki Yamaguchi⁶, Shouichi Ohga⁷, Atsushi Manabe⁸, Hideo Harigae⁹, Shinji Kunishima⁴, Eiichi Ishii¹⁰, Masao Kobayashi¹¹, Kenichi Koike¹², Kenichiro Watanabe¹³, Etsuro Ito¹⁴, Minoru Takata¹⁵, Miharu Yabe¹⁶, Seishi Ogawa², Satoru Miyano^{3

17}, Seiji Kojima¹

Affiliations

¹ Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁴ Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
⁵ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
⁶ Department of Hematology, Nippon Medical School, Tokyo, Japan.
⁷ Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
⁸ Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
⁹ Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai, Japan.
¹⁰ Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
¹¹ Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
¹² Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
¹³ Department of Hematology/Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
¹⁴ Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
¹⁵ Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan.
¹⁶ Department of Cell Transplantation and Regenerative Medicine, Tokai University Hospital, Isehara, Japan.
¹⁷ Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

PMID: 28102861
DOI: 10.1038/gim.2016.197

Free article

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

Hideki Muramatsu et al. Genet Med. 2017 Jul.

Free article

. 2017 Jul;19(7):796-802.

doi: 10.1038/gim.2016.197. Epub 2017 Jan 19.

Authors

Affiliations

¹ Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁴ Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
⁵ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
⁶ Department of Hematology, Nippon Medical School, Tokyo, Japan.
⁷ Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
⁸ Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
⁹ Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai, Japan.
¹⁰ Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
¹¹ Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
¹² Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
¹³ Department of Hematology/Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
¹⁴ Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
¹⁵ Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan.
¹⁶ Department of Cell Transplantation and Regenerative Medicine, Tokai University Hospital, Isehara, Japan.
¹⁷ Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

PMID: 28102861
DOI: 10.1038/gim.2016.197

Abstract

Purpose: 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.

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

Results: 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.

Conclusion: 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.

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References

1. Haematologica. 2015 Jan;100(1):42-8 - PubMed
1. Blood. 2009 Jun 25;113(26):6549-57 - PubMed
1. Blood. 2014 Oct 30;124(18):2812-9 - PubMed
1. Blood. 2013 May 30;121(22):e138-48 - PubMed
1. Nat Genet. 1999 Oct;23(2):166-75 - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

References

MeSH terms

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Medical