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
Endocrinology & Metabolism
Rachel Willimann, Christina Chougar, Lawrence C. Wolfe, Lionel Blanc, Jeffrey M. Lipton
Summary: In recent years, there has been a growing body of research on the interaction between bone and bone marrow in relation to anemia. This review discusses four heritable clinical syndromes that contrast anemia affecting bone growth and development with abnormal bone development leading to anemia, highlighting the complex interactions between skeletal development and hematopoiesis.
CURRENT OSTEOPOROSIS REPORTS
(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)
Review
Hematology
Inderjeet Dokal, Hemanth Tummala, Tom Vulliamy
Summary: Inherited bone marrow failure syndromes are a group of diseases characterized by diverse manifestations and involvement of bone marrow failure. Significant progress has been made in the genetics of these diseases, revealing how genetic mutations disrupt normal hematopoiesis. Furthermore, these studies provide insights into human development and cancer. Genetic testing facilitates accurate diagnosis in clinical practice. Current treatment options have improved patient outcomes, but managing certain complications remains challenging.
Review
Hematology
Deena Iskander, Noemi B. A. Roy, Elspeth Payne, Emma Drasar, Kelly Hennessy, Yvonne Harrington, Chrysi Christodoulidou, Anastasios Karadimitris, Leisa Batkin, Josu de la Fuente
Summary: Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome caused by gene mutations. The disease is characterized by anemia, congenital anomalies, and increased risk of cancer. Diagnosis and management of DBA in older adolescents and adults are discussed in this review, based on published literature, clinical experience, and input from affected families.
Article
Biochemistry & Molecular Biology
Derek A. Franklin, Shijie Liu, Aiwen Jin, Pengfei Cui, Zengli Guo, Kyle C. Arend, Nathaniel J. Moorman, Shenghui He, Gang Greg Wang, Yisong Y. Wan, Yanping Zhang
Summary: Recent discovery of the RP-MDM2-p53 signaling pathway implicates the role of p53 in ribosomopathies. Conditional RPL11 deletion in mice results in embryonic lethality or acute anemia depending on the stage of deletion. Mechanistically, RPL11 haploinsufficiency activates p53, impeding erythroid precursor differentiation and causing insufficient red blood cell development. Reducing p53 dosage or blocking the RP-MDM2-p53 pathway rescues the anemia phenotype in mice. These findings highlight the critical role of the RP-MDM2-p53 pathway in maintaining RP homeostasis and the molecular basis for RP deficiency-associated anemia.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Senthil Velan Bhoopalan, Jonathan S. Yen, Thiyagaraj Mayuranathan, Kalin D. Mayberry, Yu Yao, Maria Angeles Lillo Osuna, Yoonjeong Jang, Janaka S. S. Liyanage, Lionel Blanc, Steven R. Ellis, Marcin W. Wlodarski, Mitchell J. Weiss
Summary: Diamond-Blackfan anemia (DBA) is a genetic blood disease caused by heterozygous loss-of-function mutations in ribosomal protein genes, resulting in hypoplastic anemia and later multilineage cytopenias. A tractable experimental model of DBA was created through genome editing of human HSPCs, revealing associated hematopoietic stem cell defects in the disease.
Review
Medicine, General & Internal
Moritz Dorenkamp, Naomi Porret, Miriam Diepold, Alicia Rovo
Summary: This article presents a rare case of Diamond-Blackfan anemia (DBA) in a 21-year-old woman who developed severe symptomatic anemia. Although a congenital syndrome had been suspected since birth, a confirmation diagnosis was not made until the patient sought medical evaluation. Molecular investigation revealed a mutation in the RPL5 gene, confirming the DBA diagnosis. The unusual evolution of this case is discussed and the literature is revisited.
MEDICINA-LITHUANIA
(2023)
Review
Pediatrics
Kaitlyn M. Dorn, Kaitlyn D. Burns, Maija A. R. Trout, D. Isum Ward, KayeLyn J. Wagner, Lauritz R. Meyer, Michelle L. Baack, Rachel L. Rodel
Summary: This case presents a male neonate with severe anemia at birth, confirmed by rWES to have Diamond-Blackfan anemia along with his mother. It emphasizes the importance of fetal surveillance and the clinical utility of rWES in the neonatal intensive care setting.
Article
Oncology
Daria Fedorova, Galina Ovsyannikova, Maria Kurnikova, Anna Pavlova, Tatiana Konyukhova, Alexey Pshonkin, Nataliya Smetanina
Summary: This study reports two patients with a DBA-like phenotype who have germline de novo variants in the TP53 gene. Both patients became transfusion independent after L-leucine therapy. Therefore, the possible role of TP53 variants should be considered in patients with a DBA-like phenotype without mutations in RP genes.
PEDIATRIC BLOOD & CANCER
(2022)
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
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.
Review
Pediatrics
Iordanis Pelagiadis, Ioannis Kyriakidis, Nikolaos Katzilakis, Chrysoula Kosmeri, Danai Veltra, Christalena Sofocleous, Stavros Glentis, Antonis Kattamis, Alexandros Makis, Eftichia Stiakaki
Summary: Diamond-Blackfan anemia (DBA) is a ribosomopathy characterized by bone marrow erythroid hypoplasia and severe anemia in infancy. In addition to classic DBA, other variations have been identified. Splice variants are common in DBA and have a significant impact on ribosome translation and levels. This study presents two cases with novel pathogenic splice variants.
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
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)