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Pathogenetic Aspects of the Ribosomopathy Shwachman–Diamond Syndrome
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Pathogenetic Aspects of the Ribosomopathy Shwachman–Diamond Syndrome

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 2971

Special Issue Editors

Dr. Annalisa Frattini

E-Mail Website
Guest Editor
Biomedical and Genetics Research Institute, National Council of Research, 20090 Milano, Italy
Interests: human rare diseases; bone diseases; stem cells; mouse model
Prof. Francesco Pasquali

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Insubria, 21100 VARESE (VA), Italy
Interests: cytogenetics; medical genetics; cytogenetics in oncohematology; Shwachman-Diamond Syndrome
Dr. Roberto Valli

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Insubria, 21100 VARESE (VA), Italy
Interests: cytogenomics; molecular genetics; inherited bone marrow failure sybdromes (IBMFS); Shwachman-Diamond Syndrome

Special Issue Information

Dear Colleagues,

Shwachman–Diamond syndrome (SDS) is a rare multi-system disorder, principally characterized by exocrine pancreatic insufficiency, skeletal abnormalities, and bone marrow failure, with high risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The inheritance is usually autosomal recessive, and SBDS is the major causative gene. More recently, other genes have been found to be associated with the disease. SDS is a ribosomopathy, as the molecular functions of all the genes involved are linked to the ribosome maturation pathway, but the complete picture of the pathogenesis has yet to be clarified. Routine cytogenetics of the bone marrow may be crucial to achieve early identification of any possible signs of evolution to MDS or AML. Some peculiar bone marrow chromosome anomalies have been linked to a better prognosis due to somatic molecular rescue mechanisms. The treatment of patients is mainly based on a symptomatic approach, but new possible drugs focused on the pathogenesis of the disease have been proposed.

This Special Issue is dedicated to all the fields of research on the pathogenetic aspects of SDS.

Dr. Annalisa Frattini
Prof. Francesco Pasquali
Dr. Roberto Valli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Shwachman–Diamond Syndrome (SDS)
  • ribosomopathy
  • cytogenetics
  • molecular mechanisms of pathogenesis
  • SDS therapy
  • SDS and hematology

Published Papers (1 paper)

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Research

17 pages, 3609 KiB  
Article
Enhanced p53 Levels Are Involved in the Reduced Mineralization Capacity of Osteoblasts Derived from Shwachman–Diamond Syndrome Subjects
by Annalisa Frattini, Simona Bolamperti, Roberto Valli, Marco Cipolli, Rita Maria Pinto, Elena Bergami, Maria Rita Frau, Simone Cesaro, Michela Signo, Valentino Bezzerri, Giovanni Porta, Abdul Waheed Khan, Alessandro Rubinacci and Isabella Villa
Int. J. Mol. Sci. 2021, 22(24), 13331; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413331 - 11 Dec 2021
Cited by 4 | Viewed by 2367
Abstract
Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show [...] Read more.
Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced SBDS gene expression and reduced/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs. Whole transcriptome analysis showed significant differences in the gene expression of SDS-OBs vs. H-OBs, particularly in the ossification pathway. SDS-OBs expressed lower levels of the main genes responsible for osteoblastogenesis. Of all downregulated genes, Western blot analyses confirmed lower levels of alkaline phosphatase and collagen type I in SDS-OBs than in H-OBs. Interestingly, SDS-OBs showed higher protein levels of p53, an inhibitor of osteogenesis, compared to H-OBs. Silencing of Tp53 was associated with higher collagen type I and alkaline phosphatase protein levels and an increase in SDS-OB mineralization capacity. In conclusion, our results show that the reduced capacity of SDS-OBs to mineralize is mediated, at least in part, by the high levels of p53 and highlight an important role of SBDS in osteoblast functions. Full article
(This article belongs to the Special Issue Pathogenetic Aspects of the Ribosomopathy Shwachman–Diamond Syndrome)
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