Article
Biochemistry & Molecular Biology
Elena Spinetti, Pietro Delre, Michele Saviano, Dritan Siliqi, Gianluca Lattanzi, Giuseppe Felice Mangiatordi
Summary: Shwachman-Diamond Syndrome (SDS) is a rare genetic disease with no specific treatment currently available. This study used comparative molecular dynamics simulations to analyze three SBDS mutants and found that both an open and closed conformation of SBDS are necessary for its proper function, providing new insights into SDS pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Huihan Tan, Dequan Su, Zhiqiang Zhuo
Summary: This study analyzed the genetic abnormalities and clinical manifestations of SDS, showing that elevated transaminase and restricted growth are common initial symptoms. Genetic testing is helpful for diagnosis.
Article
Multidisciplinary Sciences
Alyssa L. Kennedy, Kasiani C. Myers, James Bowman, Christopher J. Gibson, Nicholas D. Camarda, Elissa Furutani, Gwen M. Muscato, Robert H. Klein, Kaitlyn Ballotti, Shanshan Liu, Chad E. Harris, Ashley Galvin, Maggie Malsch, David Dale, John M. Gansner, Taizo A. Nakano, Alison Bertuch, Adrianna Vlachos, Jeffrey M. Lipton, Paul Castillo, James Connelly, Jane Churpek, John R. Edwards, Nobuko Hijiya, Richard H. Ho, Inga Hofmann, James N. Huang, Sioban Keel, Adam Lamble, Bonnie W. Lau, Maxim Norkin, Elliot Stieglitz, Wendy Stock, Kelly Walkovich, Steffen Boettcher, Christian Brendel, Mark D. Fleming, Stella M. Davies, Edie A. Weller, Christopher Bahl, Scott L. Carter, Akiko Shimamura, R. Coleman Lindsley
Summary: Research on germline genetic leukemia predisposition in Shwachman-Diamond syndrome identified early emergence of multiple hematopoietic clones with EIF6 or TP53 mutations. The germline SBDS deficiency constrains clone selection via compensatory EIF6 inactivation and maladaptive TP53 mutations, with subsequent leukemia linked to biallelic TP53 alterations. These findings offer insights into clinical surveillance strategies.
NATURE COMMUNICATIONS
(2021)
Review
Pediatrics
Xue Han, Shuanglong Lu, Changjuan Gu, Zhuli Bian, Xiaotian Xie, Xiaohong Qiao
Summary: Pancreatic exocrine insufficiency and growth failure were common initial symptoms of SDS. SDS onset occurred early in childhood with significant individual differences. Comprehensive collection and analysis of case-related data can facilitate clinicians' understanding of the clinical characteristics of SDS, leading to improved early diagnosis and effective clinical intervention.
Article
Genetics & Heredity
Ibrahim Taha, Federica De Paoli, Selena Foroni, Susanna Zucca, Ivan Limongelli, Marco Cipolli, Cesare Danesino, Ugo Ramenghi, Antonella Minelli
Summary: This study investigates the clinical variability in two siblings with Shwachman-Diamond Syndrome (SDS) carrying the same SBDS mutations. Whole-exome sequencing was performed and a novel de novo variant in the KMT2A gene was found in one sibling, which is associated with Wiedemann-Steiner Syndrome. These findings suggest that other germline variants, in addition to SBDS mutation, may contribute to the clinical variability observed in SDS patients.
Review
Oncology
Fares Bou Mitri, Blandine Beaupain, Jean-Francois Flejou, Matthieu Patient, Ilona Okhremchuck, Didier Blaise, Faezeh Izadifar-Legrand, Jean Alain Martignoles, Francois Delhommeau, Christine Bellanne-Chantelot, Jean-Francois Emile, Jean Donadieu
Summary: Shwachman-Diamond syndrome with Shwachman-Bodian-Diamond syndrome (SBDS) biallelic variants is a rare disorder that predisposes carriers to malignant hemopathies, with limited understanding of solid-cancer predisposition. Solid tumors were identified in three out of 155 cases in the French Registry for Severe Chronic Neutropenia, occurring predominantly in adults during the fifth decade and resulting in rapid fatal outcomes despite localized diagnosis. No cancers were observed post transplantation in the 14 HSCT survivors, indicating a potential link between the syndrome and solid cancer development in adults.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Pediatrics
Samuele Naviglio, Antonio Giacomo Grasso, Chiara Iacono, Giada Zanella, Valentina Kiren, Nagua Giurici, Federico Verzegnassi, Natalia Maximova, Marco Rabusin
Summary: Shwachman-Diamond syndrome is a rare bone marrow failure syndrome characterized by pancreatic insufficiency, bone abnormalities, and increased risk of MDS and AML. Venetoclax has shown promise in treating AML in elderly adults, but there is limited evidence on its use in pediatric patients with SDS-related MDS or AML.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biochemistry & Molecular Biology
Laura Peretto, Elena Tonetto, Iva Maestri, Valentino Bezzerri, Roberto Valli, Marco Cipolli, Mirko Pinotti, Dario Balestra
Summary: Shwachman-Diamond syndrome (SDS) is a common inherited bone marrow failure syndrome caused by SBDS gene mutations. The mutation in the SBDS c.258+2T>C variant affects splicing, but some correct transcripts can still be produced, explaining the survival of SDS patients. Correction approaches at the RNA and DNA levels, such as engineered U1snRNA, trans-splicing, and base/prime editors, can partially counteract the mutation effect and lead to correctly spliced transcripts. DNA editors, in particular, may offer a potential innovative therapy for SDS by reverting the mutation and potentially selecting bone-marrow cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Jianguo Zhao, Chen Zhang, Feng Liu, Gary J. Cheng
Summary: This study utilized molecular dynamics simulation to investigate the effects of femtosecond laser on the internal structure of diamond, revealing that femtosecond laser internal scribing can transform diamond into an amorphous structure while maintaining the same strength. Furthermore, the local high temperature and high pressure induced by femtosecond laser are the primary reasons for the phase transition.
Article
Genetics & Heredity
Ibrahim Taha, Selena Foroni, Roberto Valli, Annalisa Frattini, Pamela Roccia, Giovanni Porta, Marco Zecca, Elena Bergami, Marco Cipolli, Francesco Pasquali, Cesare Danesino, Claudia Scotti, Antonella Minelli
Summary: A reanalysis of available WES files of SDS patients with biallelic SBDS pathogenic variants was performed, and the results were studied using next bioinformatic and protein structural analysis. Clinical attention was given to the patient focused in this study.
FRONTIERS IN GENETICS
(2022)
Review
Pediatrics
Lusine V. Navasardyan, Ingrid Furlan, Stephanie Brandt, Ansgar Schulz, Martin Wabitsch, Christian Denzer
Summary: In this case report, a 5-year-old girl with SDS who underwent bone marrow transplantation developed autoantibody-positive type 1 diabetes mellitus at the age of 1.8 years. The manifestation and course of diabetes development were mild, with concurrent spontaneous episodes of hypoglycemia even before the onset of antidiabetic treatment. Adequate metabolic control can currently be achieved by dietary intervention.
ITALIAN JOURNAL OF PEDIATRICS
(2023)
Article
Hematology
Sangmoon Lee, Chang Hoon Shin, Jawon Lee, Seong Dong Jeong, Che Ry Hong, Jun-Dae Kim, Ah-Ra Kim, Boryeong Park, Soo Jin Son, Oleksandr Kokhan, Taekyeong Yoo, Jae Sung Ko, Young Bae Sohn, Ok-Hwa Kim, Jung Min Ko, Tae-Joon Cho, Nathan T. Wright, Je Kyung Seong, Suk-Won Jin, Hyoung Jin Kang, Hyeon Ho Kim, Murim Choi
Summary: This study presents three unrelated Korean SDS patients with biallelic pathogenic variants in EFL1, generated from bone marrow-specific somatic uniparental disomy in chromosome 15. These recombination events resulted in homozygosity for a relatively milder variant, which could evade catastrophic physiologic consequences but still impair 80S ribosome assembly and induce SDS features. Loss of EFL1 led to inhibition of terminal oligopyrimidine element-containing ribosomal protein transcript 80S assembly, proposing a more accurate pathogenesis mechanism of EFL1 dysfunction in SDS.
Article
Anesthesiology
Semih Degerli
Summary: Shwachman-Diamond syndrome is a rare genetic disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal deformities, and potential immune, hepatic, and cardiac disorders. Treatment includes pancreatic enzymes, fat-soluble vitamins, and granulocyte-colony stimulating factor. Patients may have pancreatic lipomatosis, neutropenia, and be at increased risk for developing aplastic anemia or leukemia. Skeletal manifestations include short stature, rib cage dysplasia, metaphyseal dysostosis, and osteoporosis. Even with treatment, most patients with SDS remain short in stature.
ANASTHESIOLOGIE & INTENSIVMEDIZIN
(2021)
Article
Endocrinology & Metabolism
Agnieszka Bogusz-Wojcik, Honorata Kolodziejczyk, Elzbieta Moszczynska, Maja Klaudel-Dreszler, Grzegorz Oracz, Joanna Pawlowska, Mieczyslaw Szalecki
Summary: Endocrine dysfunctions, especially growth hormone deficiency, are common in Shwachman-Diamond syndrome (SDS) patients. Both boys and girls with SDS showed significantly lower height and BMI, delayed bone age, and osteopaenia. Longitudinal studies are needed for a better understanding of the etiology and true prevalence of these disorders.
ENDOKRYNOLOGIA POLSKA
(2021)
Article
Pharmacology & Pharmacy
Qiuhong Li, Kexin Chen, Tianyi Zhang, Donghui Jiang, Ligang Chen, Jun Jiang, Chunxiang Zhang, Shengbiao Li
Summary: Sorafenib is a key first-line treatment for liver cancer with a well-known safety profile. Although novel first-line drugs may have better efficacy, they also have limitations such as worse safety and cost-effectiveness. In addition to inducing apoptosis, Sorafenib can trigger ferroptosis, which has recently been recognized as immunogenic cell death, providing new possibilities for cancer treatment. Resistance to Sorafenib-induced ferroptosis remains a major challenge.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
