Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
New Sights: Genetic Advances and Challenges in Rare Diseases
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

New Sights: Genetic Advances and Challenges in Rare Diseases

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: 20 November 2024 | Viewed by 4816

Special Issue Editor

Dr. Luisa M. Botella

E-Mail Website
Guest Editor
Centro de Investigaciones Biológicas, Margarita Salas (CSIC), 28040 Madrid, Spain
Interests: genetics; TGF-β; vascular disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is a pleasure to introduce this Special Issue.  

Rare diseases (RDs) have lower incidence rates. Typically, RDs are mostly underdiagnosed, with a few active studies, and lack therapeutic options. Eighty percent of the RDs are genetic. RDs cover a broad range of disorders, with more than 7000 different ones. Around 6–8% of the world population is affected by some RD. The advent of Genetics Advances has sped up early diagnosis and family screening processes, contributing to appropriate patient follow-ups and preventing undesired outcomes. Thus, Genetics is a major tool for diagnosis and clinical prevention. Genetic Advances empower researchers to apply a personalized approach to the diagnosis and molecular basis of these diseases. Knowing that the genes/pathways are altered, we can search for targeted therapies in a precise/personalized manner. Some undiagnosed diseases need Genetic Advances to identify the cause of the pathology. Rare tumors have also a genetic basis. This Special Issue aims to highlight the current Genetic Advances and how they are improving the diagnosis of RD and the molecular basis of diseases to search for tailored therapies. Thus, in vitro and in vivo results on therapeutic targets will be also a highly appreciated.

Dr. Luisa M. Botella
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

  • rare diseases
  • cavernomas
  • NGS
  • exome/genome
  • epigenome, undiagnosed rare diseases
  • phenotype–genotype correlations
  • transcription regulation
  • biomarkers
  • personalized medicine, precision medicine

Published Papers (3 papers)

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

Research

12 pages, 679 KiB  
Article
Investigation of the Genetic Determinants of Telangiectasia and Solid Organ Arteriovenous Malformation Formation in Hereditary Hemorrhagic Telangiectasia (HHT)
by Kevin J. Whitehead, Doruk Toydemir, Whitney Wooderchak-Donahue, Gretchen M. Oakley, Bryan McRae, Angelica Putnam, Jamie McDonald and Pinar Bayrak-Toydemir
Int. J. Mol. Sci. 2024, 25(14), 7682; https://doi.org/10.3390/ijms25147682 - 12 Jul 2024
Viewed by 363
Abstract
Telangiectases and arteriovenous malformations (AVMs) are the characteristic lesions of Hereditary Hemorrhagic Telangiectasia (HHT). Somatic second-hit loss-of-function variations in the HHT causative genes, ENG and ACVRL1, have been described in dermal telangiectasias. It is unclear if somatic second-hit mutations also cause the [...] Read more.
Telangiectases and arteriovenous malformations (AVMs) are the characteristic lesions of Hereditary Hemorrhagic Telangiectasia (HHT). Somatic second-hit loss-of-function variations in the HHT causative genes, ENG and ACVRL1, have been described in dermal telangiectasias. It is unclear if somatic second-hit mutations also cause the formation of AVMs and nasal telangiectasias in HHT. To investigate the genetic mechanism of AVM formation in HHT, we evaluated multiple affected tissues from fourteen individuals. DNA was extracted from fresh/frozen tissue of 15 nasal telangiectasia, 4 dermal telangiectasia, and 9 normal control tissue biopsies, from nine unrelated individuals with HHT. DNA from six formalin-fixed paraffin-embedded (FFPE) AVM tissues (brain, lung, liver, and gallbladder) from five individuals was evaluated. A 736 vascular malformation and cancer gene next-generation sequencing (NGS) panel was used to evaluate these tissues down to 1% somatic mosaicism. Somatic second-hit mutations were identified in three in four AVM biopsies (75%) or half of the FFPE (50%) samples, including the loss of heterozygosity in ENG in one brain AVM sample, in which the germline mutation occurred in a different allele than a nearby somatic mutation (both are loss-of-function mutations). Eight of nine (88.9%) patients in whom telangiectasia tissues were evaluated had a somatic mutation ranging from 0.68 to 1.96% in the same gene with the germline mutation. Six of fifteen (40%) nasal and two of four (50%) dermal telangiectasia had a detectable somatic second hit. Additional low-level somatic mutations in other genes were identified in several telangiectasias. This is the first report that nasal telangiectasias and solid organ AVMs in HHT are caused by very-low-level somatic biallelic second-hit mutations. Full article
(This article belongs to the Special Issue New Sights: Genetic Advances and Challenges in Rare Diseases)
►▼ Show Figures

Figure 1

12 pages, 2131 KiB  
Article
Pilot Study by Liquid Biopsy in Gastrointestinal Stromal Tumors: Analysis of PDGFRA D842V Mutation and Hypermethylation of SEPT9 Presence by Digital Droplet PCR
by Rocío Olivera-Salazar, Gabriel Salcedo Cabañas, Luz Vega-Clemente, David Alonso-Martín, Víctor Manuel Castellano Megías, Peter Volward, Damián García-Olmo and Mariano García-Arranz
Int. J. Mol. Sci. 2024, 25(12), 6783; https://doi.org/10.3390/ijms25126783 - 20 Jun 2024
Viewed by 594
Abstract
Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential [...] Read more.
Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists’ diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes. Full article
(This article belongs to the Special Issue New Sights: Genetic Advances and Challenges in Rare Diseases)
►▼ Show Figures

Figure 1

14 pages, 4323 KiB  
Article
Molecular and Cellular Characterization of Primary Endothelial Cells from a Familial Cavernomatosis Patient
by Laura Lorente-Herraiz, Angel M. Cuesta, Jaime Granado, Lucía Recio-Poveda, Luisa-María Botella and Virginia Albiñana
Int. J. Mol. Sci. 2024, 25(7), 3952; https://doi.org/10.3390/ijms25073952 - 2 Apr 2024
Viewed by 3580
Abstract
Cerebral cavernous malformation (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2 [...] Read more.
Cerebral cavernous malformation (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2, CCM3) and its origin (spontaneous or familial), different types of this disease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression profiles of these cells were analyzed and compared to primary ECs from a healthy donor. The mutation of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased expression of genes involved in intercellular junction formation, angiogenesis, and vascular homeostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and somewhat predisposed to vascular damage. Full article
(This article belongs to the Special Issue New Sights: Genetic Advances and Challenges in Rare Diseases)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop