Article
Genetics & Heredity
Ke An, Jing-Bo Zhou, Yao Xiong, Wei Han, Tao Wang, Zhi-Qiang Ye, Yun-Dong Wu
Summary: This study comprehensively investigated the structural basis of DBA mutations of RPS19 using computational methods, revealing how these mutations destabilize RPS19 or disrupt RPS19-RNA interaction to contribute to the pathogenesis of DBA. Additionally, a machine-learning model was trained to predict the pathogenicity of RPS19 mutations, laying a foundation for understanding the pathogenesis of DBA from a structural perspective.
FRONTIERS IN GENETICS
(2021)
Article
Physiology
Beren Karaosmanoglu, M. Alper Kursunel, Duygu Uckan Cetinkaya, Fatma Gumruk, Gunes Esendagli, Sule Unal, Ekim Z. Taskiran
Summary: Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome caused mainly by mutations in ribosomal protein genes. Studies have shown that DBA patients have distinct transcriptomic profiles in certain bone marrow cells, particularly in proerythroblasts, indicating functional impairment in erythroid differentiation. Additionally, patients with mutations in RPS19 and CECR1 may share common transcriptomic signatures, suggesting a potential role of inflammatory bone marrow niche in DBA pathogenesis.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Genetics & Heredity
Noemy Piantanida, Marta La Vecchia, Marika Sculco, Maria Talmon, Gioele Palattella, Ryo Kurita, Yukio Nakamura, Antonella Ellena Ronchi, Irma Dianzani, Steven R. Ellis, Luigia Grazia Fresu, Anna Aspesi
Summary: In this study, we characterized the phenotype of RPS26-deficiency in a human erythroid progenitor cell line and demonstrated that these cells can be used as a model system to study aspects of Diamond Blackfan anemia pathophysiology.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Shan Liu, Kunlin Pei, Lu Chen, Jing Wu, Qiuling Chen, Jinyan Zhang, Hui Zhang, Chengyi Wang
Summary: This is a case report of a 5-year-old boy with anemia of unknown etiology. Whole-exome sequencing revealed a de novo GATA1 c.220 + 1G>C mutation. Reporter gene assay showed that this mutation did not affect GATA1 transcriptional activity. However, normal GATA1 transcription was disturbed with increased expression of the shorter isoform. RDDS prediction analysis suggested that abnormal GATA1 splicing might be the underlying mechanism disrupting GATA1 transcription, leading to impaired erythropoiesis. Prednisone treatment significantly improved erythropoiesis, as evidenced by increased hemoglobin and reticulocyte counts.
FRONTIERS IN GENETICS
(2023)
Article
Hematology
Pedro Gonzalez-Menendez, Ira Phadke, Meagan E. Olive, Axel Joly, Julien Papoin, Hongxia Yan, Jeremy Galtier, Jessica Platon, Sun Woo Sophie Kang, Kathy L. McGraw, Marie Daumur, Marie Pouzolles, Taisuke Kondo, Stephanie Boireau, Franciane Paul, David J. Young, Sylvain Lamure, Raghavendra G. Mirmira, Anupama Narla, Guillaume Cartron, Cynthia E. Dunbar, Myriam Boyer-Clavel, Natalie Porat-Shliom, Valerie Dardalhon, Valderie S. Zimmermann, Marc Sitbon, Thomas E. Dever, Narla Mohandas, Lydie Da Costa, Namrata D. Udeshi, Lionel Blanc, Sandrina Kinet, Naomi Taylor
Summary: This study demonstrates that metabolic programs play a role in the fate of hematopoietic stem and progenitor cells (HSPCs), and the metabolic regulation of protein synthesis controls HSPC differentiation. The researchers found that the uptake of arginine and its catabolism to spermidine control erythroid specification of HSPCs through the activation of eIF5A. The study also reveals the importance of mitochondrial translation and oxidative phosphorylation in eIF5A-regulated erythropoiesis. Rating: 8/10
Article
Cell Biology
Husam Qanash, Yongqin Li, Richard H. Smith, Kaari Linask, Sara Young-Baird, Waleed Hakami, Keyvan Keyvanfar, John S. Choy, Jizhong Zou, Andre Larochelle
Summary: Diamond Blackfan Anemia (DBA) is a congenital macrocytic anemia associated with ribosomal protein haploinsufficiency. The FDA-approved drug eltrombopag shows promise in improving anemia in DBA patients by restricting the labile iron pool derived from excessive free heme.
Article
Biochemistry & Molecular Biology
Maria Sona Jerome, Dechamma Pandyanda Nanjappa, Anirban Chakraborty, Sanjiban Chakrabarty
Summary: Ribosomopathies are rare congenital disorders caused by genetic variations in ribosome-related proteins, resulting in defective ribosome biogenesis. This leads to nucleolar stress response, impaired protein synthesis, and tissue-specific phenotypes. In addition, defects in mitochondrial ribosome biogenesis affect multiple organs. Deregulated ribosomal function is also observed in certain human malignancies. This article highlights the clinical conditions, affected genes, implicated pathways, and current treatment strategies for these disorders.
Review
Oncology
Senthil Velan Bhoopalan, Shruthi Suryaprakash, Akshay Sharma, Marcin W. Wlodarski
Summary: Diamond-Blackfan anemia is a common genetic cause of bone marrow failure in children, characterized by anemia and bone marrow hypoplasia. It is associated with congenital anomalies, immunodeficiency, and increased risk of malignancies. Corticosteroids provide temporary relief for anemia, but most patients require lifelong blood transfusions. Allogeneic hematopoietic cell transplantation is a potential curative option, but with significant risks. Autologous genetic therapies are being developed to address the lack of suitable donors.
FRONTIERS IN ONCOLOGY
(2023)
Article
Pediatrics
Nicole Vogel, Markus Schmugge, Raffaele Renella, Nicolas Waespe, Heinz Hengartner
Summary: Diamond-Blackfan anemia (DBA) is a rare genetic disorder caused by mutations in ribosomal subunit genes, leading to macrocytic anemia and congenital malformations. A retrospective study of 17 pediatric DBA patients in Switzerland revealed a wide range of clinical presentations and treatment needs, with patients carrying RPL mutations showing more physical malformations and milder anemia compared to RPS mutation carriers.
EUROPEAN JOURNAL OF PEDIATRICS
(2021)
Article
Oncology
Satoru Takafuji, Takeshi Mori, Noriyuki Nishimura, Nobuyuki Yamamoto, Suguru Uemura, Kandai Nozu, Kiminori Terui, Tsutomu Toki, Etsuro Ito, Hideki Muramatsu, Yoshiyuki Takahashi, Masafumi Matsuo, Tomohiko Yamamura, Kazumoto Iijima
Summary: This study presents functional splicing analysis results of deep intronic variants in the pathogenic gene RPS19 of Diamond-Blackfan anemia (DBA), with one variant leading to exon 6 skipping. Minigene assay analysis of three previously reported deep intronic variants showed no aberrant splicing. Therefore, the minigene assay is an effective method for functional splicing analysis of inherited diseases.
PEDIATRIC HEMATOLOGY AND ONCOLOGY
(2021)
Article
Genetics & Heredity
Simon Lebaron, Marie-Francoise O'donohue, Scott C. Smith, Kendra L. Engleman, Jane Juusola, Nicole P. Safina, Isabelle Thiffault, Carol J. Saunders, Pierre-Emmanuel Gleizes
Summary: This study reports an atypical clinical case of Diamond-Blackfan anemia (DBA) associated with a missense variant in the RPL8 gene. Functional studies showed that these variants affect ribosome production and are likely pathogenic. The study suggests including RPL8 in the list of DBA-associated genes.
Review
Biochemistry & Molecular Biology
Jeanne Rakotopare, Franck Toledo, Alfonso Baldi
Summary: Studies on both animal models and humans have revealed that mutations affecting p53 activity can lead to features of certain bone marrow failure syndromes, including dyskeratosis congenita, Diamond-Blackfan anemia, and Fanconi anemia. p53 regulates multiple genes related to these syndromes, forming a positive feedback loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Isabel S. Naarmann-de Vries, Roberta Senatore, Bodo Moritz, Gernot Marx, Henning Urlaub, Dierk Niessing, Dirk H. Ostareck, Antje Ostareck-Lederer
Summary: Post-transcriptional control is crucial for the structural and metabolic changes in enucleated reticulocytes during terminal maturation to functional erythrocytes. HNRNPK regulates the timely synthesis of ALOX15, which initiates mitochondria degradation, by inhibiting translation initiation. HNRNPK interferes with 80S ribosome assembly by interacting differentially with RPS19, affecting ALOX15 synthesis and mitochondria degradation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell & Tissue Engineering
Mark C. Wilkes, Hee-Don Chae, Vanessa Scanlon, Alma-Martina Cepika, Ethan P. Wentworth, Mallika Saxena, Ascia Eskin, Zugen Chen, Bert Glader, Maria Grazia Roncarolo, Stanley F. Nelson, Kathleen M. Sakamoto
Summary: Diamond Blackfan anemia (DBA) is a genetic bone marrow failure syndrome characterized by severe anemia, congenital malformations, and an increased cancer risk. The downregulation of the SATB1 protein in patients and cell models of DBA leads to a reduction in the expansion of megakaryocyte/erythroid progenitors (MEPs). However, SATB1 is still important for the upregulation of erythroid factors like heat shock protein 70 (HSP70) and GATA1 during MEP differentiation, through its binding to specific sites surrounding the HSP70 genes and promoting chromatin loops necessary for their induction.
Article
Biotechnology & Applied Microbiology
Brendan Panici, Hosei Nakajima, Colleen M. Carlston, Hakan Ozadam, Can Cenik, Elif Sarinay Cenik
Summary: This study presents the first RNA expression and splicing analysis of a family with a non-canonical intronic variant in RPL11, revealing a complex disruption pattern and novel junctions. The mutation is causative for Diamond Blackfan Anemia (DBA) with incomplete penetrance and variable expressivity in the family. Coordinated expression between mitochondrial components and RPL11 was found to be lost in all carriers, potentially contributing to the variable expressivity of the disease.