Year: 2012
Type: article
Study design: Observational Study
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.
Source: Blood
Authors: Madoka Kuramitsu, Aiko Sato-Otsubo, Tomohiro Morio, Masatoshi Takagi, Tsutomu Toki, Kiminori Terui, RuNan 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 Takizawa, Takuo Mizukami, Kazunari Yamaguchi, Seishi Ogawa, Etsuro Ito, Isao Hamaguchi
Institutions: National Institute of Infectious Diseases, The University of Tokyo, Tokyo Medical and Dental University, Hirosaki University, Tokyo Women's Medical University, Kyushu University, Toho University, Nagoya University, Shiga Medical Center for Children, University of Yamanashi, Shizuoka Children's Hospital, Seirei Hamamatsu General Hospital, Kushiro City General Hospital, Gifu University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Development of analysis for multidrug resistance protein 1 (MRP1) modulator, The study on the mechanisms of leukemogenesis caused by qualitative and quantitative abnormalities of GATA1 transcription factor, Identification and Characterization of a Hematopoietic Stem Cell Niche in Spleen, Development of novel gene therapy for congenital blood disorders using induced pluripotent stem cells, Research on the pathogenesis and treatment of Epstein-Barr virusassociated intractable diseases, Analysis for the association of autophagy with diamond blackfan anemia associated genes.
OpenAlex ID: W2051293920