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 Sanada2,4, 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 Miyano3,17, Seiji Kojima1. 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.
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.
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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