30 results on '"Shwachman-Diamond syndrome"'
Search Results
2. Diabetes/ Endocrine Surveillance in SDS
- Author
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Shwachman Diamond Syndrome Foundation and Barnes-Jewish Hospital
- Published
- 2024
3. Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
- Author
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Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Marrow Donor Program, and National Heart, Lung, and Blood Institute (NHLBI)
- Published
- 2024
4. CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
- Author
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Diane George, Assistant Professor of Pediatrics
- Published
- 2024
5. Baby Detect : Genomic Newborn Screening
- Author
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Centre Hospitalier Régional de la Citadelle, University of Liege, Sanofi, Orchard Therapeutics, Takeda, Zentech-Lacar Company, Leon Fredericq Foundation, and Laurent Servais, Professor
- Published
- 2024
6. Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
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- 2024
7. Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
- Published
- 2024
8. Shwachman–Diamond syndrome due to biallelic EFL1 variants with complex and fatal clinical course in early infancy.
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Cario, Holger, Bertrand, Alexis, Tan, Shengjiang, Auber, Bernd, Erlacher, Miriam, Mair, Eva‐Maria, Hardenberg, Sandra, Lebrecht, Dirk, Revy, Patrick, and Warren, Alan J.
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GENETIC variation , *PROTEIN synthesis , *BONE marrow , *FUNCTIONAL analysis , *CELL lines - Abstract
Summary Shwachman–Diamond syndrome represents a clinically and genetically heterogeneous disorder. We report on an infant with a very severe, fatal clinical course caused by biallelic EFL1 variants: c.89A>G, p.(His30Arg), and c.2599A>G, p.(Asn867Asp). Functional analysis of patient‐derived B‐lymphoblastoid and SV40‐transformed fibroblast cell lines suggests that the compound heterozygous EFL1 variants impaired mature ribosome formation leading to compromised protein synthesis, ultimately resulting in a severe form of Shwachman–Diamond syndrome. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman–Diamond syndrome.
- Author
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Lagos‐Monzon, Alejandra, Ng, Stephanie, Luca, Alice M., Li, Hongbing, Sabanayagam, Mathura, Benicio, Mariana, Moshiri, Houtan, Armstrong, Richard, Tailor, Chetan, Kennedy, Marion, Grunebaum, Eyal, Keller, Gordon, and Dror, Yigal
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PLURIPOTENT stem cells , *HEMATOPOIETIC stem cells , *HUMAN stem cells , *BONE marrow , *CELL analysis - Abstract
Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human‐derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation‐related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel.
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Yeshareem, Lital, Yacobovich, Joanne, Lebel, Asaf, Noy‐Lotan, Sharon, Dgany, Orly, Krasnov, Tanya, Berger Pinto, Galit, Oniashvili, Nino, Mardoukh, Jacques, Bielorai, Bella, Laor, Ruth, Mandel‐Shorer, Noa, Ben Barak, Ayelet, Levin, Carina, Asleh, Mahdi, Miskin, Hagit, Revel‐Vilk, Shoshana, Levin, Dror, Benish, Marganit, and Zuckerman, Tsila
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GRANULOCYTE-colony stimulating factor , *HEMATOPOIETIC stem cell transplantation , *MOLECULAR diagnosis , *MYELOID differentiation factor 88 - Abstract
Background: Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity. Objective: To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel. Methods: We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild‐type ELANE/G6PC3 were referred for next‐generation sequencing. Results: Sixty‐five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman–Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte‐colony stimulating factor or due to myeloid transformation. Conclusions: The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow‐up. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature.
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Veltra, Danai, Marinakis, Nikolaos M., Kotsios, Ioannis, Delaporta, Polyxeni, Kekou, Kyriaki, Kosma, Konstantina, Traeger-Synodinos, Joanne, and Sofocleous, Christalena
- Subjects
DNA analysis ,CESAREAN section ,ANEMIA ,MYELODYSPLASTIC syndromes ,STAPHYLOCOCCAL diseases ,DIFFERENTIAL diagnosis ,FETAL growth retardation ,FAMILY history (Medicine) ,PERINATAL death ,PRENATAL diagnosis ,SEVERITY of illness index ,THROMBOCYTOPENIA ,BIOINFORMATICS ,GENE expression ,SHOCK (Pathology) ,HEMOLYTIC anemia ,DISEASE relapse ,RESPIRATORY distress syndrome ,ASPHYXIA neonatorum ,GENETIC mutation ,SHWACHMAN-Diamond Syndrome ,GENOTYPES ,GENETIC testing ,NEUTROPENIA ,SEQUENCE analysis ,PHENOTYPES ,DISEASE complications ,SYMPTOMS - Abstract
Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic anemia. Life-threatening complications include progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), critical deep-tissue infections and asphyxiating thoracic dystrophy. In most patients, SDS results from biallelic pathogenic variants in the SBDS gene, different combinations of which contribute to heterogenous clinical presentations. Null variants are not well tolerated, supporting the theory that the loss of SBDS expression is likely lethal in both mice and humans. A novel complex genotype (SBDS:c.[242C>G;258+2T>C];[460-1G>A]/WFS1:c.[2327A>T];[1371G>T]) was detected in a family with recurrent neonatal deaths. A female neonate died three hours after birth with hemolytic anemia, and a male neonate with severe anemia, thrombocytopenia and neutropenia succumbed on day 40 after Staphylococcus epidermidis infection. A subsequent review of the literature focused on fatal complications, complex SBDS genotypes and/or unusual clinical presentations and disclosed rare cases, of which some had unexpected combinations of genetic and clinical findings. The impact of pathogenic variants and associated phenotypes is discussed in the context of data sharing towards expanding scientific expert networks, consolidating knowledge and advancing an understanding of novel underlying genotypes and complex phenotypes, facilitating informed clinical decisions and disease management. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Shwachman-Diamond 综合征 1 例报告及文献复习.
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李春雨, 赵艳飞, 安阳, 陈焕玲, and 姜慧轶
- Abstract
Objective: To discuss the clinical characteristics, diagnosis, and treatment of ShwachmanDiamond syndrome (SDS), and to enhance the clinicians' awareness of the disease. Methods: The clinical materials of one patient diagnosed with SDS, primarily presented with neutropenia and elevated transaminase levels, confirmed by genetic testing were retrospectively analyzed. The clinical manifestations, genetic features, diagnosis, and treatment methods of SDS were analyzed complemented with the relevant literatures. Results: This patient was a male child, aged 27 months. His initial clinical presentations were neutropenia and elevated transaminase levels. The patient had previously experienced diarrhea when the patient was 3 months old, which improved after treated with oral pancreatic enzyme dispersion. Over the past six months, the patient had recurrent respiratory infections. Upon admission, the examination results showed there was dental enamel hypoplasia, and the imaging results showed the abnormal bone density in the long bones of the limbs. The genetic sequencing results showed a homozygous mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene (c. 258+2T>C). During hospitalization, the patient received the hepatoprotective care and granulocyte augmentation supportive treatment, leading to an improvement in his condition, and the patient was discharged. During a one-year follow-up, the patient's condition was stable. Conclusion: The typical presentation of the SDS patient includes diarrhea, liver function abnormalities, hematologic abnormalities, and skeletal anomalies, particularly neutropenia; there may also be developmental delays and involvement of the heart, liver, central nervous system, skeleton, and immune system. The genetic testing of suspected children is crucial, and it can aid in the early diagnosis and treatment of SDS patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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13. Angeborene Enteropathien
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de Laffolie, Jan, Stricker, Sebastian, Zimmer, Klaus-Peter, Reinhardt, Dietrich, Series Editor, Zimmer, Klaus-Peter, Series Editor, Felderhoff-Müser, Ursula, Series Editor, Krägeloh-Mann, Ingeborg, Series Editor, Weiß, Michael, Series Editor, de Laffolie, Jan, editor, Weber, Stefanie, editor, and Reinshagen, Konrad, editor
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- 2024
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14. Growth Charts for Shwachman–Diamond Syndrome at Ages 0 to 18 Years.
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Pegoraro, Anna, Bezzerri, Valentino, Tridello, Gloria, Brignole, Cecilia, Lucca, Francesca, Pintani, Emily, Danesino, Cesare, Cesaro, Simone, Fioredda, Francesca, and Cipolli, Marco
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BODY mass index , *RESEARCH funding , *BODY weight , *HUMAN growth , *DESCRIPTIVE statistics , *STATURE , *BONE marrow diseases , *FAILURE to thrive syndrome , *SHWACHMAN-Diamond Syndrome , *ADOLESCENCE , *CHILDREN - Abstract
Simple Summary: In this study, we drew up the growth charts of Italian patients with Shwachman–Diamond syndrome (SDS) at ages 0 to 18 years. We found that the 50th and 3rd percentiles of weight and height of the pediatric general population correspond to the 97th and 50th percentiles of patients with SDS, respectively. The median age at menarche in females with SDS was comparable with that of the general population. The percentage increment in weight of subjects aged 14–18 years was higher in patients with SDS than in the general population. This study provides insight into the potential usefulness of SDS-specific growth chart data as a resource for clinicians working with patients with SDS. Shwachman–Diamond syndrome (SDS) is one of the most common inherited bone marrow failure syndromes. SDS is characterized by hypocellular bone marrow, with a severe impairment of the myeloid lineage, resulting in neutropenia, thrombocytopenia, and, more rarely, anemia. Almost 15% of patients with SDS develop myelodysplastic syndrome or acute myeloid leukemia as early as childhood or young adulthood. Exocrine pancreatic insufficiency is another common feature of SDS. Almost all patients with SDS show failure to thrive, which is associated with skeletal abnormalities due to defective ossification. Considering these observations, it remains unfeasible to use the common growth charts already available for the general population. To address this issue, we report how we drew up growth charts of patients with SDS aged 0 to 18 years. We analyzed height, weight, and body max index (BMI) in 121 Italian patients with SDS. Results indicated that the 50th and 3rd percentiles of weight and height of the pediatric general population correspond to the 97th and 50th percentiles of patients with SDS aged 0–18 years, respectively. In addition, the percentage increment in weight of subjects aged 14–18 years was higher in patients with SDS than in the general population. SDS-specific growth charts, such as those described here, afford a new tool, which is potentially useful for both clinical and research purposes in SDS. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Inherited bone marrow failure syndromes: phenotype as a tool for early diagnostic suspicion at a major reference center in Mexico.
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Leal-Anaya, Paula, Kimball, Tamara N., Lucia Yanez-Felix, Ana, Fiesco-Roa, Moisés Ó., García-de Teresa, Benilde, Monsiváis, Angélica, Juárez-Velázquez, Rocío, Lieberman, Esther, Villarroel, Camilo, Yokoyama, Emiy, Fernández-Hernández, Liliana, Rivera-Osorio, Anet, Sosa, David, Ortiz Sandoval, Maria Magdalena, López-Santiago, Norma, Frías, Sara, del Castillo, Victoria, and Rodríguez, Alfredo
- Abstract
Introduction: The inherited bone marrow failure syndromes (IBMFSs) are a group of rare disorders characterized by bone marrow failure (BMF), physical abnormalities, and an increased risk of neoplasia. The National Institute of Pediatrics (INP) is a major medical institution in Mexico, where patients with BMF receive a complete approach that includes paraclinical tests. Readily recognizable features, such as the hematological and distinctive physical phenotypes, identified by clinical dysmorphologists, remain crucial for the diagnosis and management of these patients, particularly in circumstances where next-generation sequencing (NGS) is not easily available. Here, we describe a group of Mexican patients with a high clinical suspicion of an IBMFS. Methods: We performed a systematic retrospective analysis of the medical records of patients who had a high IBMFS suspicion at our institution from January 2018 to July 2021. An initial assessment included first ruling out acquired causes of BMF by the Hematology Department and referral of the patient to the Department of Human Genetics for physical examination to search for specific phenotypes suggesting an IBMFS. Patients with high suspicion of having an IBMFS were classified into two main groups: 1) specific IBMFS, including dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS), thrombocytopenia with absent radii (TAR), and severe congenital neutropenia (SCN); 2) undefined IBMFS (UI). Results: We established a high suspicion of having an IBMFS in 48 patients. At initial evaluation, the most common hematologic features were bicytopenia (20%) and aplastic anemia (16%); three patients received hematopoietic stem cell transplantation. Among patients with a suspicion of an IBMFS, the most common physical abnormality was minor craniofacial features in 83% of patients and neurodevelopmental disorders in 52%. The specific suspicions that we built were DBA (31%), SDS (18%), DC (14%), TAR (4%), and SCN (4%), whereas 27% of cases remained as undefined IBMFS. SDS, TAR, and SCN were more commonly suspected at an earlier age (<1 year), followed by DBA (2 years) and DC (5 years). Conclusions: Thorough examination of reported clinical data allowed us to highly suspect a specific IBMFS in approximately 70% of patients; however, an important number of patients remained with suspicion of an undefined IBMFS. Implementation of NGS and telomere length measurement are forthcoming measures to improve IBMFS diagnosis in Mexico. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman–Diamond syndrome cells.
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Cipolli, Marco, Boni, Christian, Penzo, Marianna, Villa, Isabella, Bolamperti, Simona, Baldisseri, Elena, Frattini, Annalisa, Porta, Giovanni, Api, Martina, Selicato, Nora, Roccia, Pamela, Pollutri, Daniela, Marinelli Busilacchi, Elena, Poloni, Antonella, Caporelli, Nicole, D'Amico, Giovanna, Pegoraro, Anna, Cesaro, Simone, Oyarbide, Usua, and Vella, Antonio
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ORGANELLE formation , *BONE marrow cells , *NEUTROPHILS , *NONSENSE mutation , *CHEMOTAXIS , *EXOCRINE pancreatic insufficiency , *RIBOSOMAL proteins - Abstract
Summary: Shwachman–Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman–Bodian–Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation. Biallelic mutations in the SBDS gene are found in ~90% of SDS patients, ~55% of whom carry the c.183‐184TA>CT nonsense mutation. Several translational readthrough‐inducing drugs aimed at suppressing nonsense mutations have been developed. One of these, ataluren, has received approval in Europe for the treatment of Duchenne muscular dystrophy. We previously showed that ataluren can restore full‐length SBDS protein synthesis in SDS‐derived bone marrow cells. Here, we extend our preclinical study to assess the functional restoration of SBDS capabilities in vitro and ex vivo. Ataluren improved 80S ribosome assembly and total protein synthesis in SDS‐derived cells, restored myelopoiesis in myeloid progenitors, improved neutrophil chemotaxis in vitro and reduced neutrophil dysplastic markers ex vivo. Ataluren also restored full‐length SBDS synthesis in primary osteoblasts, suggesting that its beneficial role may go beyond the myeloid compartment. Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Inherited bone marrow failure syndromes: phenotype as a tool for early diagnostic suspicion at a major reference center in Mexico
- Author
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Paula Leal-Anaya, Tamara N. Kimball, Ana Lucia Yanez-Felix, Moisés Ó. Fiesco-Roa, Benilde García-de Teresa, Angélica Monsiváis, Rocío Juárez-Velázquez, Esther Lieberman, Camilo Villarroel, Emiy Yokoyama, Liliana Fernández-Hernández, Anet Rivera-Osorio, David Sosa, Maria Magdalena Ortiz Sandoval, Norma López-Santiago, Sara Frías, Victoria del Castillo, and Alfredo Rodríguez
- Subjects
inherited bone marrow failure syndrome ,dyskeratosis congenita ,Diamond–Blackfan anemia ,Shwachman–Diamond syndrome ,thrombocytopenia with absent radii ,severe congenital neutropenia ,Genetics ,QH426-470 - Abstract
Introduction: The inherited bone marrow failure syndromes (IBMFSs) are a group of rare disorders characterized by bone marrow failure (BMF), physical abnormalities, and an increased risk of neoplasia. The National Institute of Pediatrics (INP) is a major medical institution in Mexico, where patients with BMF receive a complete approach that includes paraclinical tests. Readily recognizable features, such as the hematological and distinctive physical phenotypes, identified by clinical dysmorphologists, remain crucial for the diagnosis and management of these patients, particularly in circumstances where next-generation sequencing (NGS) is not easily available. Here, we describe a group of Mexican patients with a high clinical suspicion of an IBMFS.Methods: We performed a systematic retrospective analysis of the medical records of patients who had a high IBMFS suspicion at our institution from January 2018 to July 2021. An initial assessment included first ruling out acquired causes of BMF by the Hematology Department and referral of the patient to the Department of Human Genetics for physical examination to search for specific phenotypes suggesting an IBMFS. Patients with high suspicion of having an IBMFS were classified into two main groups: 1) specific IBMFS, including dyskeratosis congenita (DC), Diamond–Blackfan anemia (DBA), Shwachman–Diamond syndrome (SDS), thrombocytopenia with absent radii (TAR), and severe congenital neutropenia (SCN); 2) undefined IBMFS (UI).Results: We established a high suspicion of having an IBMFS in 48 patients. At initial evaluation, the most common hematologic features were bicytopenia (20%) and aplastic anemia (16%); three patients received hematopoietic stem cell transplantation. Among patients with a suspicion of an IBMFS, the most common physical abnormality was minor craniofacial features in 83% of patients and neurodevelopmental disorders in 52%. The specific suspicions that we built were DBA (31%), SDS (18%), DC (14%), TAR (4%), and SCN (4%), whereas 27% of cases remained as undefined IBMFS. SDS, TAR, and SCN were more commonly suspected at an earlier age (
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- 2024
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18. Shwachman-Diamond syndrome: A case report.
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Liu Z, Tang Q, Chen X, Huang L, Lan L, Lv Z, Yang X, and Shan Q
- Subjects
- Humans, Female, Infant, Exocrine Pancreatic Insufficiency diagnosis, Exocrine Pancreatic Insufficiency genetics, Anti-Bacterial Agents therapeutic use, Shwachman-Diamond Syndrome
- Abstract
Rationale: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive genetic disease, the diagnosis is a big challenge for clinician, as the clinical manifestations of the disease are diverse. Here, we report a girl who diagnosed with SDS with the symptoms of recurrent fever, elevated transaminase levels, and granulocytosis. The aspects of diagnosis and treatment were discussed and a literature review was conducted., Patient Concerns: A 15-month-old girl admitted to our hospital because of recurrent fever, granulocytopenia, and elevated transaminase levels., Diagnosis and Interventions: The compound heterozygous variant of Shwachman-Bodian-Diamond syndrome c.258 + 2T > C:p.84Cfs3 and c.96C > G:p.Y32* were detected after sequencing the blood samples from the patient and her parents. Finally, she was diagnosed with SDS and she was treated with compound glycyrrhizin, granulocyte-colony stimulating factor, and antibiotic in the case of co-infection., Outcomes: During the follow-up, her liver function showed the level of transaminases decreased and she rarely had infection after the age of 15 months although neutropenia is still present., Lessons: Patients with SDS lacks typical clinical symptoms, which presents a huge challenge for clinicians. Genetic testing techniques is playing an important role in the diagnosis of diseases. This patient without typical clinical manifestations such as exocrine pancreatic insufficiency and skeletal abnormality, we report this case aimed to strengthen the understanding of the disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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19. A case of co-occurring acute myeloid leukemia and relapsed diffuse large B-cell lymphoma in a young adult with Shwachman-Diamond syndrome.
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LeBlanc FR, Grier DD, Myers KC, Shimamura A, and Pommert L
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- Humans, Male, Young Adult, Lipomatosis pathology, Lipomatosis complications, Exocrine Pancreatic Insufficiency complications, Exocrine Pancreatic Insufficiency genetics, Exocrine Pancreatic Insufficiency pathology, Bone Marrow Diseases pathology, Adult, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse complications, Shwachman-Diamond Syndrome, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute complications
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- 2024
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20. [Allogeneic hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: a report of three cases and literature review].
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Feng AH, Shi JM, Fu HR, Yu J, Zheng WY, Zhu YY, Huang H, and Zhao YM
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- Humans, Male, Adult, Transplantation, Homologous, Bone Marrow Diseases therapy, Mutation, Shwachman-Diamond Syndrome, Hematopoietic Stem Cell Transplantation methods, Lipomatosis, Exocrine Pancreatic Insufficiency therapy
- Abstract
This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.
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- 2024
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21. Oh rats! Intracellular rod-like inclusions in an adolescent with Shwachman-Diamond syndrome.
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Mayhew J, Luttrell H, Barros K, Blazin L, Nichols C, Avashia-Khemka N, Lavik JP, Relich RF, Skinner D, Zhou J, Saraf A, and Khaitan A
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- Humans, Animals, Rats, Shwachman-Diamond Syndrome, Exocrine Pancreatic Insufficiency complications, Exocrine Pancreatic Insufficiency genetics, Lipomatosis genetics, Bone Marrow Diseases genetics
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- 2024
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22. Unique Pharmacokinetics for Oral Tacrolimus Administration After Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia With Shwachman-Diamond Syndrome.
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Inoue Y, Uemura Y, Kosugi S, Kanno M, and Sano F
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- Humans, Administration, Oral, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacokinetics, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Shwachman-Diamond Syndrome, Tacrolimus administration & dosage, Tacrolimus pharmacokinetics
- Abstract
Competing Interests: The authors have no conflicts of interest to declare.
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- 2024
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23. Researchers' Work from National and Kapodistrian University of Athens Focuses on Shwachman-Diamond Syndrome (Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a...).
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NEONATAL death ,RESEARCH personnel ,GENOTYPES ,SYNDROMES ,LYMPHATIC diseases - Abstract
A recent study conducted by researchers from the National and Kapodistrian University of Athens focuses on Shwachman-Diamond Syndrome (SDS), a multi-system disease characterized by exocrine pancreatic insufficiency, infantile neutropenia, and aplastic anemia. The study highlights the life-threatening complications associated with SDS, such as acute myeloid leukemia, deep-tissue infections, and thoracic dystrophy. The researchers also discuss the genetic variants and phenotypes associated with SDS, emphasizing the importance of data sharing and collaboration in advancing our understanding of the disease. The study provides valuable insights for informed clinical decisions and disease management. [Extracted from the article]
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- 2024
24. Researchers Submit Patent Application, "Methods Of Using Ehmt2 Inhibitors In Treating Or Preventing Blood Disorders", for Approval (USPTO 20240180880).
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BLOOD platelet disorders ,BLOOD protein disorders ,RESPIRATORY diseases ,BLOOD coagulation disorders ,BONE marrow diseases ,METHYLTRANSFERASES - Abstract
This document is a patent application for the use of EHMT2 inhibitors in treating or preventing various blood disorders. The inhibitors target a specific mechanism in cells and could potentially be effective in conditions such as anemia, thalassemia, leukemia, lymphoma, and sickle-cell disease. The application provides specific compounds that could be used as inhibitors and suggests that they can be used alone or in combination with other treatments. For more information, readers are directed to the full patent application. [Extracted from the article]
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- 2024
25. Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication.
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Wang L, Jin Y, Chen Y, Zhao P, Shang X, Liu H, and Sun L
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- Humans, China epidemiology, Child, Child, Preschool, Infant, Male, Adolescent, Female, Infant, Newborn, Asian People genetics, Mutation genetics, East Asian People, Shwachman-Diamond Syndrome
- Abstract
Shwachman Diamond syndrome (SDS) is a rare autosomal recessive genetic disorder and due to its complex and varied clinical manifestations, diagnosis is often delayed. The purpose of this study was to investigate the clinical manifestations and genetic characteristics of SDS in Chinese patients, in order to increase pediatricians' awareness of SDS and to allow early diagnosis. We conducted a search to identify patients presenting SBDS gene pathogenic variant in two Chinese academic databases. We analyzed and summarized the epidemiology, clinical features, gene pathogenic variants, and key points in the diagnosis and treatment of SDS. We reviewed the clinical data of 39 children with SDS from previously published articles. The interval from the onset of the first symptoms to diagnosis was very long for most of our patients. The age of presentation ranged from 1 day to 10 years (median: 3 months). However, the age of diagnosis was significantly delayed, ranging from 1 month to 14 years (median: 14 months). Hematological abnormalities were the most common presentation, 89.7% (35/39) at the beginning and 94.9% (37/39) at diagnosis of SDS. Diarrhea was the second most common clinical abnormality at the time of diagnosis. 59% (23/39) of patients had a typical history of persistent chronic diarrhea. Furthermore, hepatic enlargement or elevation of transaminase occurred in 15 cases (38.5%). 56.4% patients (22/39) had a short stature, and 17.9% (7/39) patients showed developmental delay. Additionally, twenty patients had compound heterozygous pathogenic variants of c.258 + 2T > C and c.183_ 184TA > CT. Children with SDS in China had high incidence rates of chronic diarrhea, cytopenia, short stature, and liver damage. Furthermore, SBDS c.258 + 2T > C and c.183_ 184TA > CT were the most common pathogenic variants in patients with SDS. The diagnosis of SDS can be delayed if the clinical phenotype is not recognized by the health care provider., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Jin, Chen, Zhao, Shang, Liu and Sun.)
- Published
- 2024
- Full Text
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26. Knockdown of the Shwachman-Diamond syndrome gene, SBDS, induces galectin-1 expression and impairs cell growth.
- Author
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Yamaguchi M, Sera Y, Toga-Yamaguchi H, Kanegane H, Iguchi Y, and Fujimura K
- Subjects
- Animals, Humans, Mice, Cell Proliferation, Herpesvirus 4, Human, Proteins, Shwachman-Diamond Syndrome, Benzamides, Bone Marrow Diseases genetics, Epstein-Barr Virus Infections, Exocrine Pancreatic Insufficiency genetics, Exocrine Pancreatic Insufficiency metabolism, Galectin 1 genetics, Tyrosine analogs & derivatives
- Abstract
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The depletion of SBDS protein by RNA interference has been shown to cause inhibition of cell proliferation in several cell lines. However, the precise mechanism by which the loss of SBDS leads to inhibition of cell growth remains unknown. To evaluate the impaired growth of SBDS-knockdown cells, we analyzed Epstein-Barr virus-transformed lymphoblast cells (LCLs) derived from two patients with SDS (c. 183_184TA > CT and c. 258 + 2 T > C). After 3 days of culture, the growth of LCL-SDS cell lines was considerably less than that of control donor cells. By annealing control primer-based GeneFishing PCR screening, we found that galectin-1 (Gal-1) mRNA expression was elevated in LCL-SDS cells. Western blot analysis showed that the level of Gal-1 protein expression was also increased in LCL-SDS cells as well as in SBDS-knockdown 32Dcl3 murine myeloid cells. We confirmed that recombinant Gal-1 inhibited the proliferation of both LCL-control and LCL-SDS cells and induced apoptosis (as determined by annexin V-positive staining). These results suggest that the overexpression of Gal-1 contributes to abnormal cell growth in SBDS-deficient cells., (© 2024. Japanese Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
27. A Rare Inherited Bone Marrow Failure Syndrome Disclosed by Reanalysis of the Exome Data of a Patient Evaluated for Cytopenia and Dysmorphic Features.
- Author
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Durmaz D, Aslanger AD, Yavas Abali Z, Yilmaz Y, Karaman V, Yesil Sayin G, Toksoy G, Unuvar A, and Uyguner ZO
- Subjects
- Female, Humans, Child, Preschool, Congenital Bone Marrow Failure Syndromes genetics, Exome genetics, Shwachman-Diamond Syndrome, Homozygote, Cytopenia, Bone Marrow Diseases diagnosis, Bone Marrow Diseases genetics
- Abstract
Background: Multisystemic findings of inherited bone marrow failure syndromes may cause difficulty in diagnosis. Exome sequencing (ES) helps to define the etiology of rare diseases and reanalysis offers a valuable new diagnostic approach. Herein, we present the clinical and molecular characteristics of a girl who was referred for cytopenia and frequent infections., Case Report: A 5-year-old girl with cytopenia, dysmorphism, short stature, developmental delay, and myopia was referred for genetic counseling. Reanalysis of the ES data revealed a homozygous splice-site variant in the DNAJC21 (NM_001012339.3:c.983+1G>A), causing Shwachman-Diamond Syndrome (SDS). It was shown by the RNA sequencing that exon 7 was skipped, causing an 88-nucleotide deletion., Conclusions: Precise genetic diagnosis enables genetic counseling and improves patient management by avoiding inappropriate treatment and unnecessary testing. This report would contribute to the clinical and molecular understanding of this rare type of SDS caused by DNAJC21 variants and expand the phenotypic features of this condition., Competing Interests: The authors have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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28. Characteristics of Craniofacial Morphology and Occlusion in Shwachman-Diamond Syndrome: A Case Report of a Japanese Sibling Pair.
- Author
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Takahashi M, Ariwa M, and Yamaguchi T
- Abstract
Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome gene on chromosome 7q11. Although skeletal abnormalities are a feature of SDS, no reports have focused on the craniofacial morphology of patients with SDS. Moreover, the detailed dental characteristics of SDS remain unknown. In the present case report, we evaluated the craniofacial morphology and dental findings of two patients with SDS. A Japanese adolescent sibling pair with SDS had the chief complaint of excessive overjet. Cephalometric analysis revealed similar craniofacial morphology in both patients: skeletal class I malocclusion with a hypodivergent pattern and labial inclination of the maxillary and mandibular incisors. A panoramic photograph showed the tendency of delayed permanent tooth eruption and replacement in both patients. These cases suggest that malocclusion requiring orthodontic treatment might be a feature of patients with SDS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Takahashi et al.)
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- 2024
- Full Text
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29. New Findings from Nagoya University in Shwachman-Diamond Syndrome Provides New Insights (Shwachman-diamond Syndromes: Clinical, Genetic, and Biochemical Insights From the Rare Variants).
- Abstract
A new report from Nagoya University in Japan provides insights into Shwachman-Diamond Syndrome, a rare inherited bone marrow failure syndrome. The syndrome is characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities, with a 10-30% chance of transformation to a myeloid neoplasm. The research identifies four genes, including SBDS, DNAJC21, EFL1, and SRP54, that play a role in the syndrome and are involved in ribosome biogenesis or early protein synthesis. The findings highlight the importance of this synthetic pathway in myelopoiesis. [Extracted from the article]
- Published
- 2024
30. SBDS Gene Mutation Increases ROS Production and Causes DNA Damage as Well as Oxidation of Mitochondrial Membranes in the Murine Myeloid Cell Line 32Dcl3.
- Author
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Sera Y, Yamamoto S, Mutou A, Koba S, Kurokawa Y, Imanaka T, and Yamaguchi M
- Subjects
- Animals, Mice, Cell Line, Myeloid Cells metabolism, Oxidation-Reduction, Proteins metabolism, Proteins genetics, Shwachman-Diamond Syndrome, DNA Damage, Mitochondrial Membranes metabolism, Mutation, Reactive Oxygen Species metabolism
- Abstract
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. SDS has a variety of clinical features, including exocrine pancreatic insufficiency and hematological dysfunction. Neutropenia is the most common symptom in patients with SDS. SDS is also associated with an elevated risk of developing myelodysplastic syndromes and acute myeloid leukemia. The SBDS protein is involved in ribosome biogenesis, ribosomal RNA metabolism, stabilization of mitotic spindles and cellular stress responses, yet the function of SBDS in detail is still incompletely understood. Considering the diverse function of SBDS, the effect of SBDS seems to be different in different cells and tissues. In this study, we established myeloid cell line 32Dcl3 with a common pathogenic SBDS variant on both alleles in intron 2, 258 + 2T > C, and examined the cellular damage that resulted. We found that the protein synthesis was markedly decreased in the mutant cells. Furthermore, reactive oxygen species (ROS) production was increased, and oxidation of the mitochondrial membrane lipids and DNA damage were induced. These findings provide new insights into the cellular and molecular pathology caused by SBDS deficiency in myeloid cells.
- Published
- 2024
- Full Text
- View/download PDF
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