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Genes and Variants in Human Rare Genetic Diseases
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Genes and Variants in Human Rare Genetic Diseases

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: 20 November 2024 | Viewed by 1592

Special Issue Editor

Dr. Edoardo Errichiello

E-Mail Website
Guest Editor
1. Department of Molecular Medicine, University of Pavia, Pavia, Italy
2. IRCCS Mondino Foundation, Pavia, Italy
Interests: molecular genetics; clinical genetics; next generation sequencing (NGS); molecular karyotyping; prenatal diagnosis; neurogenomics; oncogenomics; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Rare diseases (RDs) affect more than 300–400 million people worldwide, often causing chronic illness, severe disability, and premature death. In a large portion of cases, people with an undiagnosed disease incur in the so-called “diagnostic odyssey”. An accurate diagnosis of an RD can result in better clinical management, the identification of potential therapeutics, and the avoidance of unnecessary treatments that may have non-negligible side effects. In the last decade, the advent of NGS (next-generation sequencing) and omics sciences, such as genomics, transcriptomics, and methylomics, has completely revolutionized the approach to RDs.

This Special Issue aims to highlight the contribution of these novel approaches to unravel the pathogenetic mechanisms, discover novel disease genes, and depict the genetic architecture underlying RDs. Original articles, case series, reviews, and descriptions of new methodologies in the field of RDs are welcome to contribute to this Special Issue. Potential topics include, but are not limited to, the following: novel diagnostic approaches, genotype–phenotype correlations, disease gene discovery, multi-omics data integration, genetic pleiotropy, and phenotypic expansion.

We look forward to receiving your contributions.

Dr. Edoardo Errichiello
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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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 disease
  • multi-omics
  • exome
  • genome
  • transcriptome
  • methylome
  • next-generation sequencing

Published Papers (2 papers)

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16 pages, 5679 KiB  
Case Report
Identification of a Novel Indel Variant in the DARS2 Gene in Russian Patients with Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation
by Fatima M. Bostanova, Polina G. Tsygankova, Elena A. Larshina, Ilya O. Nagornov, Yulia V. Evseeva, Irina L. Krutikhina, Marina E. Dzhentemirova, Marina N. Kashlakova, Marina S. Petukhova, Inna V. Sharkova and Ekaterina Y. Zakharova
Genes 2024, 15(5), 615; https://doi.org/10.3390/genes15050615 - 11 May 2024
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Abstract
Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is an inherited disease caused by pathogenic biallelic variants in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase. This disease is characterized by slowly progressive spastic gait, cerebellar symptoms, and leukoencephalopathy [...] Read more.
Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is an inherited disease caused by pathogenic biallelic variants in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase. This disease is characterized by slowly progressive spastic gait, cerebellar symptoms, and leukoencephalopathy with brainstem and spinal cord involvement. Case Presentation: Peripheral blood samples were collected from four patients from four unrelated families to extract genomic DNA. All patients underwent partial exon analysis of the DARS2 gene using Sanger sequencing, which detected the c.228-21_228-20delinsC variant in a heterozygous state. Further DNA from three patients was analyzed using a next-generation sequencing-based custom AmpliSeq™ panel for 59 genes associated with leukodystrophies, and one of the patients underwent whole genome sequencing. We identified a novel pathogenic variant c.1675-1256_*115delinsGCAACATTTCGGCAACATTCCAACC in the DARS2 gene. Three patients (patients 1, 2, and 4) had slowly progressive cerebellar ataxia, and two patients (patients 1 and 2) had spasticity. In addition, two patients (patients 2 and 4) showed signs of axonal neuropathy, such as decreased tendon reflexes and loss of distal sensitivity. Three patients (patients 1, 2, and 3) also had learning difficulties. It should be noted the persistent presence of characteristic changes in brain MRI in all patients, which emphasizes its importance as the main diagnostic tool for suspicion and subsequent confirmation of LBSL. Conclusions: We found a novel indel variant in the DARS2 gene in four patients with LBSL and described their clinical and genetic characteristics. These results expand the mutational spectrum of LBSL and aim to improve the laboratory diagnosis of this form of leukodystrophy. Full article
(This article belongs to the Special Issue Genes and Variants in Human Rare Genetic Diseases)
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15 pages, 3590 KiB  
Case Report
Characterization of a New Variant in ARHGAP31 Probably Involved in Adams–Oliver Syndrome in a Family with a Variable Phenotypic Spectrum
by Carlo Santaniello, Alice Faversani, Luigi Corsaro, Giulia Melloni, Silvia Motta, Elena Mandorino, Davide Sacco, Sabine Stioui, Fulvio Ferrara, Davide Barteselli, Dario De Vita, Debora Manuelli and Lucy Costantino
Genes 2024, 15(5), 536; https://doi.org/10.3390/genes15050536 - 24 Apr 2024
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Abstract
Adams–Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a [...] Read more.
Adams–Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a novel variant in the ARHGAP31 gene that is predicted to result in a truncated protein with a constitutively activated catalytic site due to the loss of 688 amino acids involved in the C-terminal domain, essential for protein auto-inhibition. Pathogenic variants in ARHGAP31 exon 12, leading to a premature protein termination, are associated with Adams–Oliver syndrome. Bioinformatic analysis was useful to elucidate the impact of the identified genetic variant on protein structure. To better understand the impact of the identified variant, 3D protein models were predicted for the ARHGAP31 wild type, the newly discovered variant, and other pathogenetic alterations already reported. Our study identified a novel variant probably involved in Adams–Oliver syndrome and increased the evidence on the phenotypic variability in patients affected by this syndrome, underlining the importance of translational research, including experimental and bioinformatics analyses. This strategy represents a successful model to investigate molecular mechanisms involved in syndrome occurrence. Full article
(This article belongs to the Special Issue Genes and Variants in Human Rare Genetic Diseases)
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