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

• Published in: Genetics in medicine Vol. 19; no. 7; pp. 796 - 802
• Main Authors: Muramatsu, Hideki, Okuno, Yusuke, Yoshida, Kenichi, Shiraishi, Yuichi, Doisaki, Sayoko, Narita, Atsushi, Sakaguchi, Hirotoshi, Kawashima, Nozomu, Wang, Xinan, Xu, Yinyan, Chiba, Kenichi, Tanaka, Hiroko, Hama, Asahito, Sanada, Masashi, Takahashi, Yoshiyuki, Kanno, Hitoshi, Yamaguchi, Hiroki, Ohga, Shouichi, Manabe, Atsushi, Harigae, Hideo, Kunishima, Shinji, Ishii, Eiichi, Kobayashi, Masao, Koike, Kenichi, Watanabe, Kenichiro, Ito, Etsuro, Takata, Minoru, Yabe, Miharu, Ogawa, Seishi, Miyano, Satoru, Kojima, Seiji
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2017; Elsevier Limited
• Subjects: 631/208/2489/144; 631/208/514/2254; 692/699/1541; 692/700/139/1512; Anemia, Aplastic - diagnosis; Anemia, Aplastic - genetics; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bone Marrow Diseases - diagnosis; Bone Marrow Diseases - genetics; Bone Marrow Failure Disorders; Exome - genetics; Female; Genetic Testing; Hemoglobinuria, Paroxysmal - diagnosis; Hemoglobinuria, Paroxysmal - genetics; High-Throughput Nucleotide Sequencing - methods; High-Throughput Nucleotide Sequencing - statistics & numerical data; Human Genetics; Humans; Laboratory Medicine; Male; Mutation - genetics; original-research-article; Sequence Analysis, DNA - methods; Whole Exome Sequencing - methods; target sequencing; Fanconi anemia; next-generation sequencing; inherited bone marrow failure; whole-exome sequencing
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1038/gim.2016.197

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