Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Transcriptomics and Proteomics in RASopathies
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Transcriptomics and Proteomics in RASopathies

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 (30 April 2023) | Viewed by 1472

Special Issue Editor

Prof. Dr. Paola Riva

E-Mail Website
Guest Editor
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy
Interests: RASopathies; cancer; genetic and genomic studies; functional studies; inheritance mechanisms; molecular genetics; epigenetics

Special Issue Information

Dear Colleagues,

RASopathies are a group of disorders caused by a germline mutation generally in one of the genes encoding effectors, controlling the regulation of RAS/MAPK pathway activation. More recently, a digenic model of subclinical variants has been proposed in NS patients without a full NS mutation. This pathway is fundamental for normal development, with knockout mouse models of different components being associated with embryonic lethality. While there is an extensive literature on variants and genotypes specifically associated to RASopathies, much less is known about the extent of transcriptome, proteome, and phosphoproteome changes in this group of syndromes. This Special Issue aims to provide new insights into transcriptional, post-transcriptional, post-translational alterations and changes in phosphorylation in RASopathies, with the goal for future studies to identify the molecular mechanisms at the base of RAS pathway activation, besides potential druggable genes for the development of effectives drugs.

Prof. Dr. Paola Riva
Guest Editor

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

  • RASopathies
  • RAS pathway
  • gene expression
  • transcriptome
  • post-transcriptional regulation
  • post-translational modification
  • proteome
  • phosphoproteome

Published Papers (1 paper)

Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

14 pages, 1462 KiB  
Article
Changes of RAS Pathway Phosphorylation in Lymphoblastoid Cell Lines from Noonan Syndrome Patients Carrying Hypomorphic Variants in Two NS Genes
by Viviana Tritto, Daniele Capitanio, Cecilia Gelfi and Paola Riva
Int. J. Mol. Sci. 2023, 24(4), 4035; https://doi.org/10.3390/ijms24044035 - 17 Feb 2023
Viewed by 1242
Abstract
Noonan syndrome (NS) is an autosomal dominant multisystem disorder, characterized by variable expressivity and locus heterogeneity, being caused by mutations in one of a subset of RAS pathway genes. Nevertheless, for 20–30% of patients it is not possible to provide molecular diagnosis, suggesting [...] Read more.
Noonan syndrome (NS) is an autosomal dominant multisystem disorder, characterized by variable expressivity and locus heterogeneity, being caused by mutations in one of a subset of RAS pathway genes. Nevertheless, for 20–30% of patients it is not possible to provide molecular diagnosis, suggesting that further unknown genes or mechanisms are involved in NS pathogenesis. Recently, we proposed a digenic inheritance of subclinical variants as an alternative NS pathogenic model in two NS patients negative for molecular diagnosis. They showed hypomorphic variants of RAS pathway genes co-inherited from both their healthy parents that we hypothesized to generate an additive effect. Here, we report on the phosphoproteome and proteome analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) performed on the immortalized peripheral blood mononuclear cells (PBMCs) from the two above trios. Our results indicate that the two unrelated patients show overlapped profiles in both protein abundances and their phosphorylation levels not reached by their parents. IPA software predicted RAS-related pathways as significantly activated in the two patients. Interestingly, they remained unchanged or only slightly activated in both patients’ parents. These findings suggest that the presence of one subclinical variant can activate the RAS pathway below the pathological threshold, which can instead be exceeded by the additive effect due to the co-presence of two subclinical variants causing NS, supporting our digenic inheritance hypothesis. Full article
(This article belongs to the Special Issue Transcriptomics and Proteomics in RASopathies)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-1
Back to TopTop