title: Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes.
abstract: 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.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hideki
authors.identifier: 0000-0002-8801-0021
authors.initials: H
authors.lastname: Muramatsu
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shiraishi
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Doisaki
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Narita
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nozomu
authors.identifier: 0000-0001-5700-4481
authors.initials: N
authors.lastname: Kawashima
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Xinan
authors.identifier: 0000-0003-0024-0402
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroko
authors.identifier: 0000-0001-9634-8922
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Masashi
authors.identifier: 0000-0003-0666-1996
authors.initials: M
authors.lastname: Sanada
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hitoshi
authors.identifier: 0000-0002-0893-4030
authors.initials: H
authors.lastname: Kanno
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.identifier: 0000-0002-6698-2348
authors.initials: A
authors.lastname: Manabe
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.affiliation: Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
authors.affiliation: Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Eiichi
authors.identifier: 0000-0002-1561-2144
authors.initials: E
authors.lastname: Ishii
authors.affiliation: Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Hematology/Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
authors.forename: Kenichiro
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authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Etsuro
authors.identifier: 0000-0002-0168-2475
authors.initials: E
authors.lastname: Ito
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan.
authors.forename: Minoru
authors.identifier: 0000-0002-4926-3675
authors.initials: M
authors.lastname: Takata
authors.affiliation: Department of Cell Transplantation and Regenerative Medicine, Tokai University Hospital, Isehara, Japan.
authors.forename: Miharu
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authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoru
authors.identifier: 0000-0002-1753-6616
authors.initials: S
authors.lastname: Miyano
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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mesh_terms: D000741:Anemia, Aplastic / Q000175:diagnosis* / Q000235:genetics*; D001855:Bone Marrow Diseases / Q000175:diagnosis* / Q000235:genetics*; D000080983:Bone Marrow Failure Disorders; D059472:Exome / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D000073359:Exome Sequencing / Q000379:methods