221 results on '"Shwachman-Diamond syndrome"'
Search Results
2. Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome.
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Lagos-Monzon A, Ng S, Luca AM, Li H, Sabanayagam M, Benicio M, Moshiri H, Armstrong R, Tailor C, Kennedy M, Grunebaum E, Keller G, and Dror Y
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- Humans, Gene Expression Profiling, Phenotype, Mutation, Lipomatosis genetics, Lipomatosis pathology, Lipomatosis metabolism, Ribosomes metabolism, Ribosomes genetics, Biomarkers, Transcriptome, Proteins, Shwachman-Diamond Syndrome, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells pathology, Induced Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells cytology, Hematopoiesis, Cell Differentiation
- 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., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2024
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3. 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
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- 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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4. 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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5. Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel.
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Yeshareem L, Yacobovich J, Lebel A, Noy-Lotan S, Dgany O, Krasnov T, Berger Pinto G, Oniashvili N, Mardoukh J, Bielorai B, Laor R, Mandel-Shorer N, Ben Barak A, Levin C, Asleh M, Miskin H, Revel-Vilk S, Levin D, Benish M, Zuckerman T, Wolach O, Pazgal I, Brik Simon D, Gilad O, Yanir AD, Goldberg TA, Izraeli S, Tamary H, and Steinberg-Shemer O
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- Humans, Male, Israel epidemiology, Female, Child, Child, Preschool, Adolescent, Genetic Predisposition to Disease, Adult, Hematopoietic Stem Cell Transplantation, Infant, Consanguinity, Glucose-6-Phosphatase genetics, Alleles, Registries, High-Throughput Nucleotide Sequencing, Young Adult, Phenotype, Genetic Association Studies, Neutropenia genetics, Neutropenia congenital, Neutropenia epidemiology, Neutropenia diagnosis, Mutation, Congenital Bone Marrow Failure Syndromes genetics, Congenital Bone Marrow Failure Syndromes diagnosis
- 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., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2024
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6. [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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7. 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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8. 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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9. Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication.
- Author
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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.)
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- 2024
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10. Growth Charts for Shwachman-Diamond Syndrome at Ages 0 to 18 Years.
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Pegoraro A, Bezzerri V, Tridello G, Brignole C, Lucca F, Pintani E, Danesino C, Cesaro S, Fioredda F, and Cipolli M
- Abstract
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.
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- 2024
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11. Knockdown of the Shwachman-Diamond syndrome gene, SBDS, induces galectin-1 expression and impairs cell growth.
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Yamaguchi M, Sera Y, Toga-Yamaguchi H, Kanegane H, Iguchi Y, and Fujimura K
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- 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.)
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- 2024
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12. A Rare Inherited Bone Marrow Failure Syndrome Disclosed by Reanalysis of the Exome Data of a Patient Evaluated for Cytopenia and Dysmorphic Features.
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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
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- 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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13. Characteristics of Craniofacial Morphology and Occlusion in Shwachman-Diamond Syndrome: A Case Report of a Japanese Sibling Pair.
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Takahashi M, Ariwa M, and Yamaguchi T
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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
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14. 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 P, Kimball TN, Yanez-Felix AL, Fiesco-Roa MÓ, García-de Teresa B, Monsiváis A, Juárez-Velázquez R, Lieberman E, Villarroel C, Yokoyama E, Fernández-Hernández L, Rivera-Osorio A, Sosa D, Ortiz Sandoval MM, López-Santiago N, Frías S, Del Castillo V, and Rodríguez A
- 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., 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 Leal-Anaya, Kimball, Yanez-Felix, Fiesco-Roa, García-de Teresa, Monsiváis, Juárez-Velázquez, Lieberman, Villarroel, Yokoyama, Fernández-Hernández, Rivera-Osorio, Sosa, Ortiz Sandoval, López-Santiago, Frías, Castillo and Rodríguez.)
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- 2024
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15. SBDS Gene Mutation Increases ROS Production and Causes DNA Damage as Well as Oxidation of Mitochondrial Membranes in the Murine Myeloid Cell Line 32Dcl3.
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Sera Y, Yamamoto S, Mutou A, Koba S, Kurokawa Y, Imanaka T, and Yamaguchi M
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- 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.
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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 M, Boni C, Penzo M, Villa I, Bolamperti S, Baldisseri E, Frattini A, Porta G, Api M, Selicato N, Roccia P, Pollutri D, Marinelli Busilacchi E, Poloni A, Caporelli N, D'Amico G, Pegoraro A, Cesaro S, Oyarbide U, Vella A, Lippi G, Corey SJ, Valli R, Polini A, and Bezzerri V
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- Humans, Shwachman-Diamond Syndrome, Tumor Suppressor Protein p53 genetics, Codon, Nonsense, Myelopoiesis, Neutrophils metabolism, Chemotaxis, Ribosomes metabolism, Lipomatosis genetics, Bone Marrow Diseases genetics, Bone Marrow Diseases therapy, Exocrine Pancreatic Insufficiency genetics
- Abstract
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., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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17. Variant Allele Frequency of Pseudogene-Related Variants in Short-read Next-Generation Sequencing Data May Mislead Genetic Diagnosis: A Case of Shwachman-Diamond Syndrome.
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Lee H, Lee JA, Lee H, Lee JS, Ko JM, Kim MJ, and Seong MW
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- Humans, Shwachman-Diamond Syndrome, Gene Frequency, Pseudogenes, High-Throughput Nucleotide Sequencing
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- 2023
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18. Clinical features, epidemiology, and treatment of Shwachman-Diamond syndrome: a systematic review.
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Han X, Lu S, Gu C, Bian Z, Xie X, and Qiao X
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- Female, Humans, Infant, Male, Mutation, Phenotype, Shwachman-Diamond Syndrome, Signal Recognition Particle genetics, Bone Marrow Diseases diagnosis, Bone Marrow Diseases epidemiology, Bone Marrow Diseases genetics, Exocrine Pancreatic Insufficiency diagnosis, Exocrine Pancreatic Insufficiency epidemiology, Exocrine Pancreatic Insufficiency therapy
- Abstract
Background: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS., Methods: We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included., Results: The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years., Conclusions: Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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19. Cytogenetics in the management of bone marrow failure syndromes: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).
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Cuccuini W, Collonge-Rame MA, Auger N, Douet-Guilbert N, Coster L, and Lafage-Pochitaloff M
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- Humans, Bone Marrow Failure Disorders diagnosis, Bone Marrow Failure Disorders therapy, Bone Marrow Failure Disorders complications, Chromosome Aberrations, Cytogenetic Analysis, Intracellular Signaling Peptides and Proteins genetics, Anemia, Aplastic diagnosis, Anemia, Aplastic genetics, Anemia, Aplastic therapy, Bone Marrow Diseases diagnosis, Bone Marrow Diseases genetics, Bone Marrow Diseases therapy, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes therapy, Leukemia, Myeloid, Acute complications
- Abstract
Bone marrow failure syndromes are rare disorders characterized by bone marrow hypocellularity and resultant peripheral cytopenias. The most frequent form is acquired, so-called aplastic anemia or idiopathic aplastic anemia, an auto-immune disorder frequently associated with paroxysmal nocturnal hemoglobinuria, whereas inherited bone marrow failure syndromes are related to pathogenic germline variants. Among newly identified germline variants, GATA2 deficiency and SAMD9/9L syndromes have a special significance. Other germline variants impacting biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, may cause major syndromes including Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Bone marrow failure syndromes are at risk of secondary progression towards myeloid neoplasms in the form of myelodysplastic neoplasms or acute myeloid leukemia. Acquired clonal cytogenetic abnormalities may be present before or at the onset of progression; some have prognostic value and/or represent somatic rescue mechanisms in inherited syndromes. On the other hand, the differential diagnosis between aplastic anemia and hypoplastic myelodysplastic neoplasm remains challenging. Here we discuss the value of cytogenetic abnormalities in bone marrow failure syndromes and propose recommendations for cytogenetic diagnosis and follow-up., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Masson SAS.)
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- 2023
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20. Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants.
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Kawashima N, Oyarbide U, Cipolli M, Bezzerri V, and Corey SJ
- Subjects
- Humans, Shwachman-Diamond Syndrome, Mutation, Signal Recognition Particle genetics, Lipomatosis genetics, Lipomatosis metabolism, Lipomatosis pathology, Bone Marrow Diseases genetics, Bone Marrow Diseases pathology, Exocrine Pancreatic Insufficiency genetics, Exocrine Pancreatic Insufficiency metabolism, Exocrine Pancreatic Insufficiency pathology
- Abstract
Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. In 10-30% of cases, transformation to a myeloid neoplasm occurs. Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene located on human chromosome 7q11. Over the past several years, pathogenic variants in three other genes have been identified to cause similar phenotypes; these are DNAJC21, EFL1, and SRP54. Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas). Neurocognitive, dermatologic, and retinal changes may also be found. There are specific gene-phenotype differences. To date, SBDS, DNAJC21, and SRP54 variants have been associated with myeloid neoplasia. Common to SBDS, EFL1, DNAJC21, and SRP54 is their involvement in ribosome biogenesis or early protein synthesis. These four genes constitute a common biochemical pathway conserved from yeast to humans that involve early stages of protein synthesis and demonstrate the importance of this synthetic pathway in myelopoiesis.
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- 2023
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21. The Molecular and Genetic Mechanisms of Inherited Bone Marrow Failure Syndromes: The Role of Inflammatory Cytokines in Their Pathogenesis.
- Author
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Kawashima N, Bezzerri V, and Corey SJ
- Subjects
- Humans, Congenital Bone Marrow Failure Syndromes genetics, Shwachman-Diamond Syndrome genetics, Interferon-alpha, Intracellular Signaling Peptides and Proteins, Cytokines genetics, Dyskeratosis Congenita
- Abstract
Inherited bone marrow failure syndromes (IBMFSs) include Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia, and other rare entities such as GATA2 deficiency and SAMD9/9L mutations. The IBMFS monogenic disorders were first recognized by their phenotype. Exome sequencing has validated their classification, with clusters of gene mutations affecting DNA damage response (Fanconi anemia), ribosome structure (Diamond-Blackfan anemia), ribosome assembly (Shwachman-Diamond syndrome), or telomere maintenance/stability (dyskeratosis congenita). The pathogenetic mechanisms of IBMFSs remain to be characterized fully, but an overarching hypothesis states that different stresses elicit TP53-dependent growth arrest and apoptosis of hematopoietic stem, progenitor, and precursor cells. Here, we review the IBMFSs and propose a role for pro-inflammatory cytokines, such as TGF-β, IL-1β, and IFN-α, in mediating the cytopenias. We suggest a pathogenic role for cytokines in the transformation to myeloid neoplasia and hypothesize a role for anti-inflammatory therapies.
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- 2023
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22. Spectrum of diabetes mellitus in patients with Shwachman-Diamond syndrome: case report and review of the literature.
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Navasardyan LV, Furlan I, Brandt S, Schulz A, Wabitsch M, and Denzer C
- Subjects
- Humans, Shwachman-Diamond Syndrome, Disease Progression, Exocrine Pancreatic Insufficiency complications, Exocrine Pancreatic Insufficiency diagnosis, Exocrine Pancreatic Insufficiency genetics, Lipomatosis complications, Lipomatosis diagnosis, Lipomatosis genetics, Bone Marrow Diseases complications, Bone Marrow Diseases diagnosis, Bone Marrow Diseases therapy, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 genetics
- Abstract
Background: Shwachman-Diamond syndrome (SDS) is a rare congenital disorder caused by mutations in the SBDS gene and characterized by exocrine pancreatic deficiency, hematologic dysfunction, and skeletal growth failure. Although the hematologic features and characteristics of the somatic disorders commonly associated with SDS are well known, emerging data from case reports and patient registries suggest that SDS may also be associated with an increased risk of diabetes mellitus. However, currently available data on SDS-associated diabetes are limited and do not allow conclusions regarding prevalence and incidence rates, clinical course, and outcomes., Case Presentation: Here we report the case of a 5-year-old girl with SDS who underwent bone marrow transplantation at the age of 3 months and developed autoantibody-positive type 1 diabetes mellitus at the age of 1.8 years. The manifestation and course of diabetes development were mild, complicated by concurrent spontaneous episodes of hypoglycemia even before the onset of antidiabetic treatment. Currently, adequate metabolic control can be achieved by dietary intervention., Conclusions: Considering that the SBDS protein regulates mitosis and ribosomal biosynthesis and that its suppression may cause immunologic instability and chronic inflammation, this case provides insight into the phenotype of rare Shwachman-Diamond syndrome-associated diabetes mellitus, which may be characterized by significant age-dependent differences in clinical course., (© 2023. Società Italiana di Pediatria.)
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- 2023
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23. Severe congenital neutropenia, SRP54 pathogenicity, and a framework for surveillance.
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Fan EM, Vagher J, Meznarich JA, Ubico EM, Goteti S, Peterson D, Rayes A, and Maese LD
- Subjects
- Infant, Humans, Virulence, Mutation, Congenital Bone Marrow Failure Syndromes genetics, Shwachman-Diamond Syndrome, Signal Recognition Particle genetics, Adaptor Proteins, Signal Transducing genetics, Neutropenia genetics, Neutropenia pathology
- Abstract
Severe congenital neutropenia (SCN) is a rare disorder, often due to pathogenic variants in genes such as ELANE, HAX1, and SBDS. SRP54 pathogenic variants are associated with SCN and Shwachman-Diamond-like syndrome. Thirty-eight patients with SRP54-related SCN are reported in the literature. We present an infant with SCN, without classic Shwachman-Diamond syndrome features, who presented with recurrent bacterial infections and an SRP54 (c.349_351del) pathogenic variant. Despite ongoing granulocyte colony-stimulating factor therapy, this patient has no evidence of malignant transformation. Here we establish a framework for the future development of universal guidelines to care for this patient population., (© 2023 Wiley Periodicals LLC.)
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- 2023
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24. Systemic Lupus Erythematosus in Shwachman-Diamond Syndrome: a Novel Phenotype.
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Zhang T, Yu Z, Gao S, Wang L, and Song H
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- Humans, Shwachman-Diamond Syndrome, Phenotype, Bone Marrow Diseases, Lupus Erythematosus, Systemic
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- 2023
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25. Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: biological insights and clinical advances.
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Reilly CR and Shimamura A
- Subjects
- Humans, Shwachman-Diamond Syndrome, Neoplasm Recurrence, Local, Disease Susceptibility, Bone Marrow Diseases genetics, Bone Marrow Diseases therapy, Bone Marrow Diseases diagnosis, Exocrine Pancreatic Insufficiency genetics, Exocrine Pancreatic Insufficiency therapy, Lipomatosis genetics, Lipomatosis therapy, Myeloproliferative Disorders
- Abstract
Shwachman-Diamond syndrome (SDS) is an inherited multisystem ribosomopathy characterized by exocrine pancreatic deficiency, bone marrow failure, and predisposition to myeloid malignancies. The pathobiology of SDS results from impaired ribosomal maturation due to the deficiency of SBDS and the inability to evict the antiassociation factor eIF6 from the 60S ribosomal subunit. Clinical outcomes for patients with SDS who develop myeloid malignancies are extremely poor because of high treatment-related toxicities and a high rate of refractory disease/relapse even after allogeneic hematopoietic stem cell transplant (HSCT). Registry data indicate that outcomes are improved for patients with SDS who undergo routine bone marrow surveillance and receive an HSCT before developing an overt malignancy. However, the optimal approach to hematologic surveillance and the timing of HSCT for patients with SDS is not clearly established. Recent studies have elucidated distinct patterns of somatic blood mutations in patients with SDS that either alleviate the ribosome defect via somatic rescue (heterozygous EIF6 inactivation) or disrupt cellular checkpoints, resulting in increased leukemogenic potential (heterozygous TP53 inactivation). Genomic analysis revealed that most myeloid malignancies in patients with SDS have biallelic loss-of-function TP53 mutations. Single-cell DNA sequencing of SDS bone marrow samples can detect premalignant biallelic TP53-mutated clones before clinical diagnosis, suggesting that molecular surveillance may enhance the detection of incipient myeloid malignancies when HSCT may be most effective. Here, we review the clinical, genetic, and biologic features of SDS. In addition, we present evidence supporting the hematologic surveillance for patients with SDS that incorporates clinical, pathologic, and molecular data to risk stratify patients and prioritize transplant evaluation for patients with SDS with high-risk features., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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26. Site-specific labeling of SBDS to monitor interactions with the 60S ribosomal subunit.
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Biswas A, Peng YF, Kaushik V, and Origanti S
- Subjects
- Humans, Shwachman-Diamond Syndrome metabolism, Ribosomes metabolism, Mutation, Ribosome Subunits, Large, Eukaryotic chemistry, Proteins chemistry
- Abstract
The Shwachman-Diamond syndrome (SDS) is a rare inherited ribosomopathy that is predominantly caused by mutations in the Shwachman-Bodian-Diamond Syndrome gene (SBDS). SBDS is a ribosomal maturation factor that is essential for the release of eukaryotic translation initiation factor 6 (eIF6) from 60S ribosomal subunits during the late stages of 60S maturation. Release of eIF6 is critical to permit inter-subunit interactions between the 60S and 40S subunits and to form translationally competent 80S monosomes. SBDS has three key domains that are highly flexible and adopt varied conformations in solution. To better understand the domain dynamics of SBDS upon binding to 60S and to assess the effects of SDS-disease specific mutations, we aimed to site-specifically label individual domains of SBDS. Here we detail the generation of a fluorescently labeled SBDS to monitor the dynamics of select domains upon binding to 60S. We describe the incorporation of 4-azido-l-phenylalanine (4AZP), a noncanonical amino acid in human SBDS. Site-specific labeling of SBDS using fluorophore and assessment of 60S binding activity are also described. Such labeling approaches to capture the interactions of individual domains of SBDS with 60S are also applicable to study the dynamics of other multi-domain proteins that interact with the ribosomal subunits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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27. Counteracting the Common Shwachman-Diamond Syndrome-Causing SBDS c.258+2T>C Mutation by RNA Therapeutics and Base/Prime Editing.
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Peretto L, Tonetto E, Maestri I, Bezzerri V, Valli R, Cipolli M, Pinotti M, and Balestra D
- Subjects
- Humans, DNA genetics, Mutation, RNA Splice Sites, Alternative Splicing genetics, Gene Editing, Shwachman-Diamond Syndrome genetics, Shwachman-Diamond Syndrome therapy
- Abstract
Shwachman-Diamond syndrome (SDS) represents one of the most common inherited bone marrow failure syndromes and is mainly caused by SBDS gene mutations. Only supportive treatments are available, with hematopoietic cell transplantation required when marrow failure occurs. Among all causative mutations, the SBDS c.258+2T>C variant at the 5' splice site (ss) of exon 2 is one of the most frequent. Here, we investigated the molecular mechanisms underlying aberrant SBDS splicing and showed that SBDS exon 2 is dense in splicing regulatory elements and cryptic splice sites, complicating proper 5'ss selection. Studies ex vivo and in vitro demonstrated that the mutation alters splicing, but it is also compatible with tiny amounts of correct transcripts, which would explain the survival of SDS patients. Moreover, for the first time for SDS, we explored a panel of correction approaches at the RNA and DNA levels and provided experimental evidence that the mutation effect can be partially counteracted by engineered U1snRNA, trans-splicing, and base/prime editors, ultimately leading to correctly spliced transcripts (from barely detectable to 2.5-5.5%). Among them, we propose DNA editors that, by stably reverting the mutation and potentially conferring positive selection to bone-marrow cells, could lead to the development of an innovative SDS therapy.
- Published
- 2023
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28. [Shwachman-Diamond syndrome combined with acute leukemia of ambiguous lineage: a case report].
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Zheng D, Zhu MX, Ma L, Li QH, Dong F, Wang J, and Jing HM
- Subjects
- Humans, Shwachman-Diamond Syndrome, Acute Disease, Leukemia, Myeloid, Acute
- Published
- 2023
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- View/download PDF
29. Shwachman-Diamond syndrome: A case report.
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Tang Q, Ye XM, Yang YC, and Wen XL
- Subjects
- Humans, Shwachman-Diamond Syndrome
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
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- 2023
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30. [Allogeneic hematopoietic stem cell transplantation for MDS secondary to Shwachman-Diamond syndrome: a case report].
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Zhou M, Jiang YW, Chen JJ, Wu C, Zou BB, Chen Z, Li L, Lei P, Liu GH, Tian YY, Zhu ML, and Liu C
- Subjects
- Humans, Shwachman-Diamond Syndrome, Transplantation, Homologous, Transplantation Conditioning, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes therapy, Hematopoietic Stem Cell Transplantation
- Published
- 2023
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31. Stem Cell Transplantation in Patients Affected by Shwachman-Diamond Syndrome: Expert Consensus and Recommendations From the EBMT Severe Aplastic Anaemia Working Party.
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Cesaro S, Donadieu J, Cipolli M, Dalle JH, Styczynski J, Masetti R, Strahm B, Mauro M, Alseraihy A, Aljurf M, Dufour C, and de la Tour RP
- Subjects
- Consensus, Humans, Shwachman-Diamond Syndrome, Transplantation Conditioning methods, Anemia, Aplastic diagnosis, Hematopoietic Stem Cell Transplantation methods
- Abstract
Shwachman-Diamond syndrome is a rare disorder that can develop malignant and nonmalignant hematological complications. Overall, 10% to 20% of Shwachman-Diamond patients need hematopoietic stem cell transplantation (HSCT), but most centers have a limited experience and different approaches. The European Society for Blood and Marrow Transplantation-Severe Aplastic Anaemia Working Party promoted an expert consensus to propose recommendations regarding key issues in the management of Shwachman-Diamond patients with hematological complications. The main items identified as relevant for improving survival were: the importance of regular and structured hematologic follow-up, the potential reduction of transplant-related mortality by using reduced-intensity conditioning regimens, the limitation of total body irradiation, particularly for non-malignant severe cytopenia/bone marrow failure, the early diagnosis of clonal malignant evolution and early recognition of an indication for HSCT. Finally, the poor results of HSCT in patients with acute myeloid leukemia, irrespective of cytoreductive chemotherapy treatment received prior to transplantation, highlights the need for innovative approaches. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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32. Case Report: Heterozygous Germline Variant in EIF6 Additional to Biallelic SBDS Pathogenic Variants in a Patient With Ribosomopathy Shwachman-Diamond Syndrome.
- Author
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Taha I, Foroni S, Valli R, Frattini A, Roccia P, Porta G, Zecca M, Bergami E, Cipolli M, Pasquali F, Danesino C, Scotti C, and Minelli A
- Abstract
Background: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly characterized by exocrine pancreatic insufficiency, skeletal alterations, neutropenia, and a relevant risk of hematological transformation. At least 90% of SDS patients have pathogenic variants in SBDS, the first gene associated with the disease with very low allelic heterogeneity; three variants, derived from events of genetic conversion between SBDS and its pseudogene, SBDSP1 , provided the alleles observed in about 62% of SDS patients. Methods: We performed a reanalysis of the available WES files of a group of SDS patients with biallelic SBDS pathogenic variants, studying the results by next bioinformatic and protein structural analysis. Parallelly, careful clinical attention was given to the patient focused in this study. Results: We found and confirmed in one SDS patient a germline heterozygous missense variant (c.100T>C; p.Phe34Leu) in the EIF6 gene. This variant, inherited from his mother, has a very low frequency, and it is predicted as pathogenic, according to several in silico prediction tools. The protein structural analysis also envisages the variant could reduce the binding to the nascent 60S ribosomal. Conclusion: This study focused on the hypothesis that the EIF6 germline variant mimics the effect of somatic deletions of chromosome 20, always including the locus of this gene, and similarly may rescue the ribosomal stress and ribosomal dysfunction due to SBDS mutations. It is likely that this rescue may contribute to the stable and not severe hematological status of the proband, but a definite answer on the role of this EIF6 variant can be obtained only by adding a functional layer of evidence. In the future, these results are likely to be useful for selected cases in personalized medicine and therapy., 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 © 2022 Taha, Foroni, Valli, Frattini, Roccia, Porta, Zecca, Bergami, Cipolli, Pasquali, Danesino, Scotti and Minelli.)
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- 2022
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33. Shwachman-Diamond Syndrome With Congenital Myogenic Ptosis: Case Report of a Rare Association?
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Wang NW, Georgara N, and Khan HS
- Subjects
- Humans, Shwachman-Diamond Syndrome, Blepharoptosis diagnosis, Blepharoptosis genetics, Bone Marrow Diseases complications, Bone Marrow Diseases genetics, Exocrine Pancreatic Insufficiency complications, Exocrine Pancreatic Insufficiency genetics, Lipomatosis complications, Lipomatosis diagnosis, Lipomatosis genetics, Pancytopenia complications
- Abstract
Background: Shwachman-Diamond syndrome (SDS) is a multisystem disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. There is considerable variation in the phenotypes of SDS. We present a case of an infant presenting with SDS and left-sided ptosis., Observation: We report a case of an infant who presented with 2 episodes of severe sepsis and cytopenia, without overt symptoms of exocrine pancreatic deficiency or skeletal abnormalities. Persistent left-sided ptosis was noted in both presentations. Genetic testing confirmed the diagnosis of SDS. The left-sided ptosis was diagnosed as congenital myogenic ptosis., Conclusion: The association of ptosis and other congenital bone marrow failure syndromes is well established, but this is the first description of SDS with ptosis. This association may expand our understanding of SDS phenotypes if similar cases are reported in the future., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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34. Phenotypic Variation in Two Siblings Affected with Shwachman-Diamond Syndrome: The Use of Expert Variant Interpreter (eVai) Suggests Clinical Relevance of a Variant in the KMT2A Gene.
- Author
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Taha I, De Paoli F, Foroni S, Zucca S, Limongelli I, Cipolli M, Danesino C, Ramenghi U, and Minelli A
- Subjects
- Biological Variation, Population, Humans, Siblings, Bone Marrow Diseases genetics, Exocrine Pancreatic Insufficiency genetics, Histone-Lysine N-Methyltransferase genetics, Myeloid-Lymphoid Leukemia Protein genetics, Shwachman-Diamond Syndrome genetics
- Abstract
Introduction. Shwachman-Diamond Syndrome (SDS) is an autosomal-recessive disorder characterized by neutropenia, pancreatic exocrine insufficiency, skeletal dysplasia, and an increased risk for leukemic transformation. Biallelic mutations in the SBDS gene have been found in about 90% of patients. The clinical spectrum of SDS in patients is wide, and variability has been noticed between different patients, siblings, and even within the same patient over time. Herein, we present two SDS siblings (UPN42 and UPN43) carrying the same SBDS mutations and showing relevant differences in their phenotypic presentation. Study aim. We attempted to understand whether other germline variants, in addition to SBDS, could explain some of the clinical variability noticed between the siblings. Methods. Whole-exome sequencing (WES) was performed. Human Phenotype Ontology (HPO) terms were defined for each patient, and the WES data were analyzed using the eVai and DIVAs platforms. Results. In UPN43, we found and confirmed, using Sanger sequencing, a novel de novo variant (c.10663G > A, p.Gly3555Ser) in the KMT2A gene that is associated with autosomal-dominant Wiedemann−Steiner Syndrome. The variant is classified as pathogenic according to different in silico prediction tools. Interestingly, it was found to be related to some of the HPO terms that describe UPN43. Conclusions. We postulate that the KMT2A variant found in UPN43 has a concomitant and co-occurring clinical effect, in addition to SBDS mutation. This dual molecular effect, supported by in silico prediction, could help to understand some of the clinical variations found among the siblings. In the future, these new data are likely to be useful for personalized medicine and therapy for selected cases.
- Published
- 2022
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35. A Comparative Molecular Dynamics Study of Selected Point Mutations in the Shwachman-Bodian-Diamond Syndrome Protein SBDS.
- Author
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Spinetti E, Delre P, Saviano M, Siliqi D, Lattanzi G, and Mangiatordi GF
- Subjects
- Humans, Mutation, Point Mutation, Proteins metabolism, Shwachman-Diamond Syndrome genetics, Bone Marrow Diseases genetics, Molecular Dynamics Simulation
- Abstract
The Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disease whose majority of patients display mutations in a ribosome assembly protein named Shwachman-Bodian-Diamond Syndrome protein (SBDS). A specific therapy for treating this rare disease is missing, due to the lack of knowledge of the molecular mechanisms responsible for its pathogenesis. Starting from the observation that SBDS single-point mutations, localized in different domains of the proteins, are responsible for an SDS phenotype, we carried out the first comparative Molecular Dynamics simulations on three SBDS mutants, namely R19Q, R126T and I212T. The obtained 450-ns long trajectories were compared with those returned by both the open and closed forms of wild type SBDS and strongly indicated that two distinct conformations (open and closed) are both necessary for the proper SBDS function, in full agreement with recent experimental observations. Our study supports the hypothesis that the SBDS function is governed by an allosteric mechanism involving domains I and III and provides new insights into SDS pathogenesis, thus offering a possible starting point for a specific therapeutic option.
- Published
- 2022
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36. Unusual combination of Shwachman-Diamond syndrome and porphyria.
- Author
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Spirito A, Manca E, Guida CC, Maggio A, Savino M, Aucella F, Pettoello-Mantovani M, and Ladogana S
- Subjects
- Humans, Shwachman-Diamond Syndrome, Exocrine Pancreatic Insufficiency diagnosis, Exocrine Pancreatic Insufficiency genetics, Lipomatosis diagnosis, Lipomatosis genetics, Porphyrias
- Published
- 2022
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37. Erratum: Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis.
- Author
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Frontiers Production Office
- Abstract
[This corrects the article DOI: 10.3389/fgene.2022.870233.]., (Copyright © 2022 Frontiers Production Office.)
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- 2022
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38. Coronavirus disease 2019 and vaccination in patients with Shwachman-Diamond syndrome.
- Author
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Galletta TJ, Loveless SK, Malsch MM, Shimamura A, and Myers KC
- Subjects
- COVID-19 Vaccines adverse effects, Humans, Shwachman-Diamond Syndrome, Vaccination, Bone Marrow Diseases, COVID-19 complications, Exocrine Pancreatic Insufficiency, Neutropenia
- Abstract
Because they can experience neutropenia due to bone marrow failure, patients with Shwachman-Diamond syndrome (SDS) carry increased risk for serious infections compared with the general population; however, there has been a paucity of data on the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with SDS. We compiled results from a survey distributed to participants in the SDS Registry in May-June 2021. In this report, we describe the characteristics and outcomes of patients with SDS who had COVID-19. Patients reported a short clinical course without significant complications or cytopenias. Additionally, COVID-19 vaccines were well tolerated with minor side effects., (© 2022 Wiley Periodicals LLC.)
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- 2022
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39. Genetics and genomics of bone marrow failure syndrome.
- Author
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Kim HY, Kim HJ, and Kim SH
- Abstract
Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Here, we review the clinical and genetic features of the major forms of IBMFS and discuss their molecular genetic diagnosis. Next-generation sequencing-based gene panel testing or whole exome sequencing will help elucidate the genetic causes and underlying mechanisms of this genetically heterogeneous group of diseases.
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- 2022
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40. Case Report: Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis.
- Author
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Chirita-Emandi A, Petrescu CA, Zimbru CG, Stoica F, Marian C, Ciubotaru A, Bataneant M, and Puiu M
- Abstract
Bone marrow failure represents an umbrella diagnosis for several life-threatening disorders. In many people, the etiology remains unknown for a long time, leading to an odyssey to diagnosis, with numerous tests performed and sometimes inappropriate treatment. Biallelic pathogenic variants in the DNAJC21 gene were recently discovered to cause bone marrow failure syndrome type 3, having phenotypic overlap with Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Herein, we report an 8-year-old boy, with normal intellect, presenting bone marrow failure; growth retardation; failure to thrive; recurrent infections (including sepsis); cryptorchidia; skeletal, skin, teeth, and hair abnormalities; joint hypermobility; eczema; palpebral ptosis; high myopia; rod-cone retinal dystrophy; and short telomeres. He underwent several tests and evaluations, including genetic investigations (panel and exome sequencing), before the DNAJC21 gene was known to cause disease. Whole-genome sequencing performed at the age of 7 years, identified two novel, pathogenic, and compound heterozygous variants in the DNAJC21 gene: NM_001012339.3:c.148C>T (stopgain-maternal origin), p.Gln50
∗ and c.643_644delinsTTT (frameshift paternal origin), and p.Lys215Phefs∗ 71. He received aggressive treatments for his multisystem disease: blood cell transfusions, high-dose corticosteroids, immunoglobulins, multiple antibiotics, vitamins, growth hormone, and others. However, allogeneic hematopoietic stem cell transplantation was avoided. The clinical evolution of bone marrow failure and recurrent infections stabilized with age, yet the myopia progressed. Exocrine pancreatic insufficiency was not detected. This report widens the molecular and clinical understanding of bone marrow failure syndrome type 3. Genome sequencing directed a precise diagnosis that improved patient management and enabled family genetic counseling., 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 © 2022 Chirita-Emandi, Petrescu, Zimbru, Stoica, Marian, Ciubotaru, Bataneant and Puiu.)- Published
- 2022
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41. eIF6 rebinding dynamically couples ribosome maturation and translation.
- Author
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Jaako P, Faille A, Tan S, Wong CC, Escudero-Urquijo N, Castro-Hartmann P, Wright P, Hilcenko C, Adams DJ, and Warren AJ
- Subjects
- Animals, Mammals metabolism, Mice, Ribosome Subunits, Large, Eukaryotic genetics, Ribosome Subunits, Large, Eukaryotic metabolism, Ribosomes genetics, Ribosomes metabolism, Shwachman-Diamond Syndrome, Leukemia metabolism, Proteins metabolism
- Abstract
Protein synthesis is a cyclical process consisting of translation initiation, elongation, termination and ribosome recycling. The release factors SBDS and EFL1-both mutated in the leukemia predisposition disorder Shwachman-Diamond syndrome - license entry of nascent 60S ribosomal subunits into active translation by evicting the anti-association factor eIF6 from the 60S intersubunit face. We find that in mammalian cells, eIF6 holds all free cytoplasmic 60S subunits in a translationally inactive state and that SBDS and EFL1 are the minimal components required to recycle these 60S subunits back into additional rounds of translation by evicting eIF6. Increasing the dose of eIF6 in mice in vivo impairs terminal erythropoiesis by sequestering post-termination 60S subunits in the cytoplasm, disrupting subunit joining and attenuating global protein synthesis. These data reveal that ribosome maturation and recycling are dynamically coupled by a mechanism that is disrupted in an inherited leukemia predisposition disorder., (© 2022. The Author(s).)
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- 2022
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42. Identification of an asymptomatic Shwachman-Bodian-Diamond syndrome mutation in a patient with acute myeloid leukemia.
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Shibata S, Inano S, Watanabe M, Fujiwara K, Ueno H, Nannya Y, Kanda J, Kawasaki N, Okamoto Y, Takiuchi Y, Fukunaga A, Tabata S, Ogawa S, Takaori-Kondo A, and Kitano T
- Subjects
- DNA metabolism, DNA Repair drug effects, Female, Genes, Recessive genetics, Humans, Leukemia, Myeloid, Acute drug therapy, Middle Aged, Myelodysplastic Syndromes etiology, Shwachman-Diamond Syndrome complications, Topoisomerase Inhibitors adverse effects, Germ-Line Mutation genetics, Leukemia, Myeloid, Acute etiology, Leukemia, Myeloid, Acute genetics, Proteins genetics, Shwachman-Diamond Syndrome genetics
- Abstract
Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. SDS is typically caused by a pathogenic mutation in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Patients with SDS have an increased risk of developing acute myeloid leukemia (AML) and myelodysplastic syndromes. We identified germline biallelic SBDS mutations (p.K62X and p.I167M) in a 50-year-old AML patient who had never experienced the typical symptoms of SDS. The K62X mutation is one of the most common pathogenic mutations, whereas the significance of the I167M mutation was unclear. Based on cellular experiments, we concluded that the I167M mutation contributed to the development of AML, and chemotherapy including topoisomerase inhibitors, which induce DNA double-strand breaks, may have been toxic to this patient. Our experience indicates that some asymptomatic Shwachman-Bodian-Diamond syndrome mutations contribute to the development of leukemia, and that careful treatment selection may be warranted for patients harboring these mutations., (© 2021. Japanese Society of Hematology.)
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- 2022
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43. Atypical Findings of Shwachman-Diamond Syndrome in Early Infancy: A Diagnostic Challenge.
- Author
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Marsico C, Scozzarella A, Capretti MG, Carfagnini F, Facchini E, Arcuri S, and Aceti A
- Abstract
Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by hematological abnormalities, exocrine pancreatic insufficiency, and skeletal dysplasia. We describe a 2-month-old girl with intrauterine and extrauterine growth restriction who presented with an isolated severe anemia requiring red blood cell transfusion, without gastrointestinal symptoms, history of infection, or congenital abnormalities. An abdominal ultrasound revealed a reduced pancreatic thickness and abnormal echogenicity without fat infiltration, further confirmed by MRI. Because of this peculiar pancreatic appearance, pancreatic function was investigated and revealed exocrine insufficiency. Genetic testing confirmed SDS diagnosis. The typical clinical, laboratory, and imaging features of SDS are often lacking in the first months of life, and this may delay diagnosis. In early infancy, low birth weight and lack of catch-up growth, isolated hematological abnormalities other than neutropenia and atypical pancreatic imaging may lead to SDS diagnosis even when the most common diagnostic criteria are not fulfilled., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
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- 2022
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44. Hematologic complications with age in Shwachman-Diamond syndrome.
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Furutani E, Liu S, Galvin A, Steltz S, Malsch MM, Loveless SK, Mount L, Larson JH, Queenan K, Bertuch AA, Fleming MD, Gansner JM, Geddis AE, Hanna R, Keel SB, Lau BW, Lipton JM, Lorsbach R, Nakano TA, Vlachos A, Wang WC, Davies SM, Weller E, Myers KC, and Shimamura A
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Humans, Infant, Middle Aged, Shwachman-Diamond Syndrome, Young Adult, Bone Marrow Diseases complications, Bone Marrow Diseases genetics, Bone Marrow Diseases pathology, Exocrine Pancreatic Insufficiency complications, Exocrine Pancreatic Insufficiency genetics, Hematologic Diseases complications
- Abstract
Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with leukemia predisposition. An understanding of the hematologic complications of SDS with age could guide clinical management, but data are limited for this rare disease. We conducted a cohort study of 153 subjects from 143 families with confirmed biallelic SBDS mutations enrolled on the North American Shwachman Diamond Registry or Bone Marrow Failure Registry. The SBDS c.258 + 2T>C variant was present in all but 1 patient. To evaluate the association between blood counts and age, 2146 blood counts were analyzed for 119 subjects. Absolute neutrophil counts were positively associated with age (P < .0001). Hemoglobin was also positively associated with age up to 18 years (P < .0001), but the association was negative thereafter (P = .0079). Platelet counts and marrow cellularity were negatively associated with age (P < .0001). Marrow cellularity did not correlate with blood counts. Severe marrow failure necessitating transplant developed in 8 subjects at a median age of 1.7 years (range, 0.4-39.5), with 7 of 8 requiring transplant prior to age 8 years. Twenty-six subjects (17%) developed a myeloid malignancy (16 myelodysplasia and 10 acute myeloid leukemia) at a median age of 12.3 years (range, 0.5-45.0) and 28.4 years (range, 14.4-47.3), respectively. A lymphoid malignancy developed in 1 patient at the age of 16.9 years. Hematologic complications were the major cause of mortality (17/20 deaths; 85%). These data inform surveillance of hematologic complications in SDS., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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45. [Haploidentical stem cell transplantation for acute myeloid leukemia associated with adult-onset Shwachman-Diamond syndrome].
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Uemura Y, Hirakawa T, Matsunawa M, Kozuki K, Saiki Y, Takimoto M, Sano F, Watanabe K, Inoue Y, and Arai A
- Subjects
- Busulfan therapeutic use, Humans, Male, Shwachman-Diamond Syndrome, Transplantation Conditioning, Whole-Body Irradiation, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
A 21-year-old man presented with bone marrow failure, short stature, fatty degeneration of the pancreas on CT images, and Shwachman-Bodian-Diamond syndrome (SBDS) gene abnormalities (exon 2: c.258+2T>C and deletion of exon 3). Thus, the patient was diagnosed with Shwachman-Diamond syndrome (SDS). In the clinical course, the patient developed acute myeloid leukemia (AML). Hematopoietic stem cell transplantation from the human-leukocytic-antigen-haploidentical father of the patient was performed. The patient was conditioned with 150 mg/m
2 fludarabine, 6.4 mg/kg busulfan, and 4 Gy total body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, micophenolate mofetil, and posttransplant cyclophosphamide. Although the patient achieved a complete remission on day 21, AML relapsed on day 434 after the transplantation. He died of sepsis. The prognosis of patients with SDS and AML is poor. Adult-onset cases must be recognized, and transplantation should be performed during bone marrow failure.- Published
- 2022
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46. Autoimmune neutropenia associated with heterozygous variant of SBDS gene mimicking Shwachman-Bodian-Diamond syndrome.
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Rother C, Gebauer N, Schneider J, Bauer A, Holzhausen F, Mayer T, Riecke A, Müller M, Merz H, Steinestel K, and Witte HM
- Subjects
- Humans, Proteins genetics, Shwachman-Diamond Syndrome, Bone Marrow Diseases diagnosis, Bone Marrow Diseases genetics, Neutropenia diagnosis, Neutropenia genetics
- Published
- 2021
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- View/download PDF
47. The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations.
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Khan AW, Kennedy A, Furutani E, Myers K, Frattini A, Acquati F, Roccia P, Micheloni G, Minelli A, Porta G, Cipolli M, Cesaro S, Danesino C, Pasquali F, Shimamura A, and Valli R
- Abstract
Background: An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of the SBDS gene. These clonal changes imply milder haematological symptoms and lower risk of myelodysplastic syndromes and acute myeloid leukaemia, thanks to already postulated rescue mechanisms., Results: Bone marrow from fourteen patients exhibiting either the i(7)(q10) or the del(20)(q) and coming from two large cohorts of patients, were subjected to chromosome analyses, Fluorescent In Situ Hybridization with informative probes and array-Comparative Genomic Hybridization. One patient with the i(7)(q10) showed a subsequent clonal rearrangement of the normal chromosome 7 across years. Four patients carrying the del(20)(q) evolved further different del(20)(q) independent clones, within a single bone marrow sample, or across sequential samples. One patient with the del(20)(q), developed a parallel different clone with a duplication of chromosome 3 long arm. Eight patients bore the del(20)(q) as the sole chromosomal abnormality. An overall overview of patients with the del(20)(q), also including cases already reported, confirmed that all the deletions were interstitial. The loss of material varied from 1.7 to 26.9 Mb and resulted in the loss of the EIF6 gene in all patients., Conclusions: Although the i(7)(q) and the del(20)(q) clones are frequent and clinically benign in Shwachman Diamond-syndrome, in the present work we show that they may rearrange, may be lost and then reconstructed de novo, or may evolve with independent clones across years. These findings unravel a striking selective pressure exerted by SBDS deficiency driving to karyotype instability and to specific clonal abnormalities., (© 2021. The Author(s).)
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- 2021
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48. Shwachman-Diamond Syndrome in a Child Presenting With Chronic Diarrhea: A Rare Case in Family Medicine Practice.
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Alshammari M, Aljohani MA, Hashash JM, Alsaedi HA, Alobaidi WY, Alhuzali NK, Alnumani MS, Alrashidi AH, Al-Battniji SA, Alotaibi NA, Alhumaidi NK, Alajaimi AN, Alqurashi RS, Albishri AT, and Alshammari KH
- Abstract
Diarrhea remains an important cause of morbidity and mortality worldwide. Chronic diarrhea often represents a diagnostic challenge for family medicine and pediatric physicians because of its broad spectrum of possible etiologies. The differential diagnoses can be narrowed by taking a detailed history and performing an appropriate physical examination. In general, chronic diarrhea can be due to osmotic, secretory, inflammatory, or dysmotility-related pathologies. We present the case of a 30-month-old male who was brought to the family medicine clinic with a complaint of abdominal bloating and persistent diarrhea after every feeding for four months. His stools were foul-smelling and occurred more than four times a day. The patient was below the second standard deviations for weight and height. He appeared pale, and there was no scleral icterus. The patient underwent upper endoscopy, which showed no abnormal gross findings. A dedicated abdominal computed tomography scan was performed to evaluate the pancreas for any structural abnormalities. The scan demonstrated complete replacement of the pancreatic parenchyma by fatty tissue. The diagnosis of Shwachman-Diamond syndrome was established as the analysis revealed a mutation in the SBDS gene. The patient was treated with pancreatic enzyme replacement therapy. After two months of follow-up, the parents reported that the patient had significant improvement in diarrhea. Shwachman-Diamond syndrome is a very rare inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. Despite its rarity, clinicians should keep a high index for this condition when they encounter a child with unexplained chronic diarrhea., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Alshammari et al.)
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- 2021
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49. Shwachman‒Diamond syndrome with initial features mimicking common variable immunodeficiency.
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Hou JW
- Subjects
- Diagnosis, Differential, Humans, Shwachman-Diamond Syndrome, Common Variable Immunodeficiency diagnosis
- Abstract
Competing Interests: Declaration of competing interest The author declares no conflict of interest.
- Published
- 2021
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50. Shwachman-Diamond syndrome and solid tumors: Three new patients from the French Registry for Severe Chronic Neutropenia and literature review.
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Bou Mitri F, Beaupain B, Flejou JF, Patient M, Okhremchuck I, Blaise D, Izadifar-Legrand F, Martignoles JA, Delhommeau F, Bellanne-Chantelot C, Emile JF, and Donadieu J
- Subjects
- Female, Humans, Registries, Neoplasms complications, Neoplasms epidemiology, Neoplasms genetics, Neutropenia epidemiology, Neutropenia etiology, Neutropenia genetics, Shwachman-Diamond Syndrome complications
- Abstract
Shwachman-Diamond syndrome with Shwachman-Bodian-Diamond syndrome (SBDS) biallelic variants is a rare disorder that predisposes the carrier to malignant hemopathies but solid-cancer predisposition is poorly known. Among 155 cases entered in the French Registry for Severe Chronic Neutropenia, three were identified with malignant solid tumors (ovary, breast, and esophagus). All cancers occurred during the fifth decade and, despite being localized at diagnosis, were rapidly fatal thereafter. No cancer was observed post transplantation in the 14 HSCT survivors. Based on the literature and our patient data, we can merely advance that this complication is predominantly diagnosed in adults., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
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