Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.1
3.5
Journals
Genes
Special Issues
Advances in Genetics of Motor Neuron Diseases
share announcement

Advances in Genetics of Motor Neuron Diseases

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

Deadline for manuscript submissions: 20 May 2024 | Viewed by 12475

Special Issue Editor

Dr. Christopher Grunseich

E-Mail Website
Guest Editor
Neurogenet Branch, National Institutes of Health (NIH), Bethesda, MD, USA
Interests: spinal and bulbar muscular atrophy; motor neuron disease; neurogenetics; amyotrophic lateral sclerosis type 4
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Motor neuron disease is a neurodegenerative condition that results in progressive atrophy and muscle loss as a consequence of motor neuron degeneration. Most cases of the disease are sporadic, and approximately 10% are familial. Progress has been made in identifying genes implicated in familial forms of the disease and identifying pathways and cellular processes that are altered by the mutations. Candidate genes with high penetrance have typically been identified through linkage analysis and next-generation sequencing, and other strategies including genome-wide association studies have been used to identify genes with low disease penetrance. The identification of genetic causes and risk factors is helpful to not only develop better models of disease and understand the pathogenesis, but also to guide the rationale and design of new avenues for therapeutic development. An example of success with this approach comes from the development of an antisense oligonucleotide (nusinersen) which can target exon 7 retention in the SMN2 gene and improve the amount of functional SMN protein in patients with spinal muscular atrophy and deletion in SMN1. Nusinersen was approved by the US Food and Drug Agency in December 2016 for the treatment of spinal muscular atrophy.

This Special Issue aims to provide a broad and updated overview of the genetics of motor neuron diseases and the resulting clinical and molecular observations which may lead to new therapeutic insights for the treatment of the disease.

Dr. Christopher Grunseich
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

  • motor neuron disease
  • familial amyotrophic lateral sclerosis (fALS)
  • gene therapy
  • antisense oligonucleotides (ASOs)
  • precision medicine
  • novel therapeutic approaches

Published Papers (6 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

Jump to: Review, Other

16 pages, 1641 KiB  
Article
PCR-Based Screening of Spinal Muscular Atrophy for Newborn Infants in Hyogo Prefecture, Japan
by Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu and Hiroyuki Awanoadd Show full author list remove Hide full author list
Genes 2022, 13(11), 2110; https://doi.org/10.3390/genes13112110 - 14 Nov 2022
Cited by 11 | Viewed by 2747 | Correction
Abstract
Spinal muscular atrophy (SMA) is a common devastating neuromuscular disorder, usually involving homozygous deletion of the SMN1 gene. Newly developed drugs can improve the motor functions of infants with SMA when treated in the early stage. To ensure early diagnosis, newborn screening for [...] Read more.
Spinal muscular atrophy (SMA) is a common devastating neuromuscular disorder, usually involving homozygous deletion of the SMN1 gene. Newly developed drugs can improve the motor functions of infants with SMA when treated in the early stage. To ensure early diagnosis, newborn screening for SMA (SMA-NBS) via PCR-based genetic testing with dried blood spots (DBSs) has been spreading throughout Japan. In Hyogo Prefecture, we performed a pilot study of SMA-NBS to assess newborn infants who underwent routine newborn metabolic screening between February 2021 and August 2022. Hyogo Prefecture has ~40,000 live births per year and the estimated incidence of SMA is 1 in 20,000–25,000 based on genetic testing of symptomatic patients with SMA. Here, we screened 8336 newborns and 12 screen-positive cases were detected by real-time PCR assay. Multiplex ligation-dependent probe amplification assay excluded ten false positives and identified two patients. These false positives might be related to the use of heparinized and/or diluted blood in the DBS sample. Both patients carried two copies of SMN2, one was asymptomatic and the other was symptomatic at the time of diagnosis. SMA-NBS enables us to prevent delayed diagnosis of SMA, even if it does not always allow treatment in the pre-symptomatic stage. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

15 pages, 3832 KiB  
Review
Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis
by Pashtun Shahim, Gina Norato, Ninet Sinaii, Henrik Zetterberg, Kaj Blennow, Leighton Chan and Christopher Grunseich
Genes 2024, 15(4), 496; https://doi.org/10.3390/genes15040496 - 16 Apr 2024
Viewed by 477
Abstract
Background: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS. Methods: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, [...] Read more.
Background: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS. Methods: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939. Results: Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival. Discussion: Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
►▼ Show Figures

Figure 1

23 pages, 651 KiB  
Review
Extracellular Vesicles as Potential Biomarkers in Amyotrophic Lateral Sclerosis
by Maruša Barbo and Metka Ravnik-Glavač
Genes 2023, 14(2), 325; https://doi.org/10.3390/genes14020325 - 27 Jan 2023
Cited by 7 | Viewed by 2093
Abstract
Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS’s slowly progressive characteristic, [...] Read more.
Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS’s slowly progressive characteristic, which is often accompanied by other neurological comorbidities, its diagnosis remains challenging. Perturbations in vesicle-mediated transport and autophagy as well as cell-autonomous disease initiation in glutamatergic neurons have been revealed in ALS. The use of extracellular vesicles (EVs) may be key in accessing pathologically relevant tissues for ALS, as EVs can cross the blood–brain barrier and be isolated from the blood. The number and content of EVs may provide indications of the disease pathogenesis, its stage, and prognosis. In this review, we collected a recent study aiming at the identification of EVs as a biomarker of ALS with respect to the size, quantity, and content of EVs in the biological fluids of patients compared to controls. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
►▼ Show Figures

Figure 1

10 pages, 467 KiB  
Review
Recommendations for Interpreting and Reporting Silent Carrier and Disease-Modifying Variants in SMA Testing Workflows
by John N. Milligan, Laura Blasco-Pérez, Mar Costa-Roger, Marta Codina-Solà and Eduardo F. Tizzano
Genes 2022, 13(9), 1657; https://doi.org/10.3390/genes13091657 - 15 Sep 2022
Cited by 6 | Viewed by 3677
Abstract
Genetic testing for SMA diagnosis, newborn screening, and carrier screening has become a significant public health interest worldwide, driven largely by the development of novel and effective molecular therapies for the treatment of spinal muscular atrophy (SMA) and the corresponding updates to testing [...] Read more.
Genetic testing for SMA diagnosis, newborn screening, and carrier screening has become a significant public health interest worldwide, driven largely by the development of novel and effective molecular therapies for the treatment of spinal muscular atrophy (SMA) and the corresponding updates to testing guidelines. Concurrently, understanding of the underlying genetics of SMA and their correlation with a broad range of phenotypes and risk factors has also advanced, particularly with respect to variants that modulate disease severity or impact residual carrier risks. While testing guidelines are beginning to emphasize the importance of these variants, there are no clear guidelines on how to utilize them in a real-world setting. Given the need for clarity in practice, this review summarizes several clinically relevant variants in the SMN1 and SMN2 genes, including how they inform outcomes for spinal muscular atrophy carrier risk and disease prognosis. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

2 pages, 178 KiB  
Correction
Correction: Noguchi et al. PCR-Based Screening of Spinal Muscular Atrophy for Newborn Infants in Hyogo Prefecture, Japan. Genes 2022, 13, 2110
by Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu and Hiroyuki Awanoadd Show full author list remove Hide full author list
Genes 2023, 14(3), 759; https://doi.org/10.3390/genes14030759 - 21 Mar 2023
Viewed by 1038
Abstract
The authors wish to make the following correction to this paper [...] Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
9 pages, 829 KiB  
Case Report
An Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with TARDBP Gene: A Case Report and Review of the Literature
by Daniel Sánchez-Tejerina, Juan Luis Restrepo-Vera, Eulalia Rovira-Moreno, Marta Codina-Sola, Arnau Llauradó, Javier Sotoca, Maria Salvado, Núria Raguer, Elena García-Arumí and Raúl Juntas-Morales
Genes 2022, 13(8), 1483; https://doi.org/10.3390/genes13081483 - 19 Aug 2022
Cited by 2 | Viewed by 1809
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can rarely affect young individuals. Juvenile ALS (JALS) is defined for individuals with an onset of the disease before the age of 25. The contribution of genetics to ALS pathology is a field of [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that can rarely affect young individuals. Juvenile ALS (JALS) is defined for individuals with an onset of the disease before the age of 25. The contribution of genetics to ALS pathology is a field of growing interest. One of the differences between adult-onset ALS and JALS is their genetic background, with a higher contribution of genetic causes in JALS. We report a patient with JALS and a pathogenic variant in the TARDBP gene (c.1035C > G; p.Asn345Lys), previously reported only in adult-onset ALS, and with an atypical phenotype of marked upper motor neuron predominance. In addition, the proband presented an additional variant in the NEK1 gene, c.2961C > G (p.Phe987Leu), which is classified as a variant of unknown significance. Segregation studies showed a paternal origin of the TARDBP variant, while the variant in NEK1 was inherited from the mother. We hypothesize that the NEK1 variant acts as a disease modifier and suggests the possibility of a functional interaction between both genes in our case. This hypothesis could explain the peculiarities of the phenotype, penetrance, and the age of onset. This report highlights the heterogeneity of the phenotypic presentation of ALS associated with diverse pathogenic genetic variants. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron 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 1-6
Back to TopTop