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, Shouichi 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 journalArticlepeer-review

47 Citations (Scopus)


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
Issue number10
Publication statusPublished - 08-03-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Extensive gene deletions in Japanese patients with diamond-blackfan anemia'. Together they form a unique fingerprint.

Cite this