Extensive gene deletions in Japanese patients with diamond-blackfan anemia

Madoka Kuramitsu, Aiko Sato-Otsubo, Tomohiro Morio, Masatoshi Takagi, Tsutomu Toki, Kiminori Terui, Ru Nan Wang, Hitoshi Kanno, Shoichi Ohga, Akira Ohara, Seiji Kojima, Toshiyuki Kitoh, Kumiko Goi, Kazuko Kudo, Tadashi Matsubayashi, Nobuo Mizue, Michio Ozeki, Atsuko Masumi, Haruka Momose, Kazuya TakizawaTakuo Mizukami, Kazunari Yamaguchi, Seishi Ogawa, Etsuro Ito, Isao Hamaguchi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2376-2384
Number of pages9
JournalBlood
Volume119
Issue number10
DOIs
Publication statusPublished - Mar 8 2012

Fingerprint

Diamond-Blackfan Anemia
Diamond
Gene Deletion
Genes
Ribosomal Proteins
Gene Dosage
Mutation
Polymorphism
Single Nucleotide Polymorphism
Exons
Japan
Screening
Nucleotides
Alleles
Phenotype
Polymerase Chain Reaction
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kuramitsu, M., Sato-Otsubo, A., Morio, T., Takagi, M., Toki, T., Terui, K., ... Hamaguchi, I. (2012). Extensive gene deletions in Japanese patients with diamond-blackfan anemia. Blood, 119(10), 2376-2384. https://doi.org/10.1182/blood-2011-07-368662

Extensive gene deletions in Japanese patients with diamond-blackfan anemia. / Kuramitsu, Madoka; Sato-Otsubo, Aiko; Morio, Tomohiro; Takagi, Masatoshi; Toki, Tsutomu; Terui, Kiminori; Wang, Ru Nan; Kanno, Hitoshi; Ohga, Shoichi; 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.

In: Blood, Vol. 119, No. 10, 08.03.2012, p. 2376-2384.

Research output: Contribution to journalArticle

Kuramitsu, M, Sato-Otsubo, A, Morio, T, Takagi, M, Toki, T, Terui, K, Wang, RN, Kanno, H, Ohga, S, Ohara, A, Kojima, S, Kitoh, T, Goi, K, Kudo, K, Matsubayashi, T, Mizue, N, Ozeki, M, Masumi, A, Momose, H, Takizawa, K, Mizukami, T, Yamaguchi, K, Ogawa, S, Ito, E & Hamaguchi, I 2012, 'Extensive gene deletions in Japanese patients with diamond-blackfan anemia', Blood, vol. 119, no. 10, pp. 2376-2384. https://doi.org/10.1182/blood-2011-07-368662
Kuramitsu M, Sato-Otsubo A, Morio T, Takagi M, Toki T, Terui K et al. Extensive gene deletions in Japanese patients with diamond-blackfan anemia. Blood. 2012 Mar 8;119(10):2376-2384. https://doi.org/10.1182/blood-2011-07-368662
Kuramitsu, Madoka ; Sato-Otsubo, Aiko ; Morio, Tomohiro ; Takagi, Masatoshi ; Toki, Tsutomu ; Terui, Kiminori ; Wang, Ru Nan ; Kanno, Hitoshi ; Ohga, Shoichi ; 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. / Extensive gene deletions in Japanese patients with diamond-blackfan anemia. In: Blood. 2012 ; Vol. 119, No. 10. pp. 2376-2384.
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AU - Toki, Tsutomu

AU - Terui, Kiminori

AU - Wang, Ru Nan

AU - Kanno, Hitoshi

AU - Ohga, Shoichi

AU - Ohara, Akira

AU - Kojima, Seiji

AU - Kitoh, Toshiyuki

AU - Goi, Kumiko

AU - Kudo, Kazuko

AU - Matsubayashi, Tadashi

AU - Mizue, Nobuo

AU - Ozeki, Michio

AU - Masumi, Atsuko

AU - Momose, Haruka

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AU - Mizukami, Takuo

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