What’s in a name?

Weiss, Mitchell J.; Mason, Philip J.

doi:10.1172/jci63989

Cited by 17 publications

(15 citation statements)

References 18 publications

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“…This landmark observation has prompted the identification by Vlachos and colleagues of much smaller deletions encompassing RPS14 that could be considered somatically 'acquired DBA' [25]. The supposition that acquired DBA may result from somatic abnormalities in RP genes as well as the recognition of cases of DBA resulting from a mutation in an erythroid-specific transcription factor has engendered some controversy and confusion as to what is DBA [119], but also points the way to the genetic assignment of the remaining genetically undetermined cases.…”

Section: Geneticsmentioning

confidence: 99%

Diamond Blackfan anemia: a model for the translational approach to understanding human disease

Vlachos

Blanc²,

Lipton³

2014

Expert Review of Hematology

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Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome. As with the other rare inherited bone marrow failure syndromes, the study of these disorders provides important insights into basic biology and, in the case of DBA, ribosome biology; the disruption of which characterizes the disorder. Thus DBA serves as a paradigm for translational medicine in which the efforts of clinicians to manage DBA have informed laboratory scientists who, in turn, have stimulated clinical researchers to utilize scientific discovery to provide improved care. In this review we describe the clinical syndrome Diamond Blackfan anemia and, in particular, we demonstrate how the study of DBA has allowed scientific inquiry to create opportunities for progress in its understanding and treatment.

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Section: Geneticsmentioning

confidence: 99%

Diamond Blackfan anemia: a model for the translational approach to understanding human disease

Vlachos

Blanc²,

Lipton³

2014

Expert Review of Hematology

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“…Two families with DBA were found to have germline X-linked GATA1 mutations by WES. Previously, GATA1 mutations were only associated with X-linked congenital dyserythropoietic anemia and thrombocytopenia (12, 78). GATA1 encodes a key component of the GATA family of transcription factors that is important in erythroid development.…”

Section: Diamond Blackfan Anemia (Dba)mentioning

confidence: 99%

Genomic Characterization of the Inherited Bone Marrow Failure Syndromes

Khincha

Savage

2013

Seminars in Hematology

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The inherited bone marrow failure syndromes (IBMFS) are a set of clinically related yet heterogeneous disorders in which at least one hematopoietic cell lineage is significantly reduced. Many of the IBMFS have notably increased cancer risks as well as other physical findings. Highly penetrant germline mutations in key pathways, such as DNA repair, telomere biology, or ribosomal biogenesis are causative of Fanconi anemia (FA), dyskeratosis congenita (DC) and Diamond-Blackfan anemia (DBA), respectively. Next-generation sequencing (NGS) generally refers to high-throughput, large-scale sequencing technologies and is being used more frequently to understand disease etiology. In the IBMFS, NGS has facilitated the discovery of germline mutations that cause thombocytopenia absent radii syndrome, a subset of DC and DBA, and other uncharacterized, but related, disorders. Panels of large numbers of genes are being used to molecularly characterize patients with IBMFS, such as FA and DBA. NGS is also accelerating the discovery of the genetic etiology of previously unclassified IBMFS. In this review, we will highlight recent studies that have employed NGS to ascertain the genetic etiology of IBMFS, namely FA, DC, DBA and TAR and discuss the translational utility of these findings.

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“…7 In an attempt to address this question, we undertook a systematic screening for novel GATA1 mutations in over 200 additional DBA patients and identified a highly informative mutation in a male patient who had received a clinical diagnosis of DBA (Fig. 1 and Supplementary Fig.…”

mentioning

confidence: 99%

Altered translation of GATA1 in Diamond-Blackfan anemia

Ludwig

Gazda

Eng

et al. 2014

Nat Med

267

336

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Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA),1,2 congenital asplenia,3 and T-cell leukemia.4 Yet how mutations in such ubiquitously expressed proteins result in cell-type and tissue specific defects remains a mystery.5 Here, we show that GATA1 mutations that reduce full-length protein levels of this critical hematopoietic transcription factor can cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can similarly reduce translation of GATA1 mRNA - a phenomenon that appears to result from this mRNA having a higher threshold for initiation of translation. In primary hematopoietic cells from patients with RPS19 mutations, a transcriptional signature of GATA1 target genes is globally and specifically reduced, confirming that the activity, but not the mRNA level, of GATA1 is reduced in DBA patients with ribosomal protein mutations. The defective hematopoiesis observed in DBA patients with ribosomal protein haploinsufficiency can be at least partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations in ubiquitous ribosomal proteins can result in human disease.

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What’s in a name?

Cited by 17 publications

References 18 publications

Diamond Blackfan anemia: a model for the translational approach to understanding human disease

Diamond Blackfan anemia: a model for the translational approach to understanding human disease

Genomic Characterization of the Inherited Bone Marrow Failure Syndromes

Altered translation of GATA1 in Diamond-Blackfan anemia

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