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菅野 仁
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Professor (Fixed Term) |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia. |
| Journal | Formal name：Blood Abbreviation：Blood ISSN code：1528-0020(Electronic)0006-4971(Linking) |
| Volume, Issue, Page | 119(10),pp.2376-84 |
| Author and coauthor | Kuramitsu Madoka, Sato-Otsubo Aiko, Morio Tomohiro, Takagi Masatoshi, Toki Tsutomu, Terui Kiminori, Wang RuNan, Kanno Hitoshi, Ohga Shouichi, Ohara Akira, Kojima Seiji, Kitoh Toshiyuki, Goi Kumiko, Kudo Kazuko, Matsubayashi Tadashi, Mizue Nobuo, Ozeki Michio, Masumi Atsuko, Momose Haruka, Takizawa Kazuya, Mizukami Takuo, Yamaguchi Kazunari, Ogawa Seishi, Ito Etsuro, Hamaguchi Isao |
| Publication date | 2012/03 |
| Summary | Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes. |
| DOI | 10.1182/blood-2011-07-368662 |
| Document No. | 22262766 |