Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia

Konno, Yasuhiko; Toki, Tsutomu; Tandai, Satoru; Xu, Gang; Wang, Ru Nan; Terui, Kiminori; Ohga, Shouichi; Hara, Toshiro; Hama, Asahito; Kojima, Seiji; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Yanagisawa, Ryu; Koike, Kenichi; Kanai, Rie; Imai, Tsuyoshi; Hongo, Teruaki; Park, Hye-Jin; Sugita, Kanji; Ito, Etsuro

doi:10.3324/haematol.2009.020826

Cited by 38 publications

(53 citation statements)

References 27 publications

(64 reference statements)

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“…15 This suggests ethnic differences in phenotypic expression; a feature that has been observed previously in other genetic diseases including Fanconi anemia. It also highlights the need to define the clinical-genetic spectrum in different ethnic populations.…”

Section: Diamond-blackfan Anemiamentioning

confidence: 58%

Inherited bone marrow failure syndromes

Dokal¹,

Vulliamy²

2010

Haematologica

110

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Section: Diamond-blackfan Anemiamentioning

confidence: 58%

Inherited bone marrow failure syndromes

Dokal¹,

Vulliamy²

2010

Haematologica

110

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“…Konno et al screened 49 Japanese patients and found that 30% (12 of 49) carried mutations. 8 In addition, our data showed that 22 of 68 DBA patients (32.4%) harbored a mutation in ribosomal protein (RP) genes (T.T., K.T., R.W., and E.I., unpublished observation, April 16, 2011). These abnormalities of RP genes cause defects in ribosomal RNA processing, formation of either the large or small ribosome subunit, and decreased levels of polysome formation, [4][5][6][9][10][11][12] which is thought to be one of the mechanisms for impairment of erythroid lineage differentiation.…”

Section: Introductionmentioning

confidence: 84%

“…Interestingly, mutations in RPS17 have been observed at a high rate (5.9%) in Japan relative to that in other countries (1%). 5,15,16 Although the percentage of DBA mutations differs among different ethnic groups, 8,[17][18][19] a certain portion of large deletions in DBA-responsible genes are likely to be determined in other countries by new strategies.…”

Section: Discussionmentioning

confidence: 99%

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Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia

Kuramitsu

Sato‐Otsubo

Morio

et al. 2012

Blood

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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. (Blood. 2012;119(10): 2376-2384)

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“…Of 68 Japanese been examined, mutations in RPS 19, RPL5, RPL11, RPS17, RPS26 were identified in 10 (14.7 %), six (8.8 %), three (4.4 %), one (1.5 %), one (1.5 %), and one (1.5 %), respectively. These mutations have subsequently been determined to occur in 32.4 % of Japanese patients [25,26]. A low incidence of mutations in the RPS19 gene may account for the overall lower incidence of total mutations in the Japanese population.…”

Section: Molecular Pathogenesismentioning

confidence: 99%

Inherited bone marrow failure syndromes in 2012

2012

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Inherited bone marrow failure syndromes (CBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignant disease. The representative diseases with trilineage involvement are Fanconi anemia and dyskeratosis congenita, while the disease with the single lineage cytopenia is DiamondBlackfan anemia. Recent advances in our understanding of these diseases have come from the identification of genetic lesions responsible for the disease and their pathways. Although recent studies have identified many causative genes, mutations of these genes have only been found in less than half of the patients. Next-generation sequencing technologies may reveal new causative genes in these patients. Also, induced pluripotent stem cells derived from patients with CBMFS will be useful to study the pathophysiology of the diseases. The only long-term curative treatment for bone marrow failure in patients with inherited bone marrow failure syndromes is allogeneic hematopoietic stem cell transplantation, although this procedure has a risk of severe adverse effects. Multicenter prospective studies are warranted to establish appropriate conditioning regimens aimed at reducing transplant-related mortality.

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Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia

Cited by 38 publications

References 27 publications

Inherited bone marrow failure syndromes

Inherited bone marrow failure syndromes

Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia

Inherited bone marrow failure syndromes in 2012

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