AI Article Synopsis
- Advances in gene therapy have expanded genetic screening for ALS to include sporadic cases, identifying genetic causes in 15% of patients.
- Screening for specific genes like C9orf72 and SOD1 reveals varying impacts on ALS symptoms, influenced by the age of onset.
- The complexity of ALS genetics, including incomplete penetrance and overlapping symptoms with other diseases, highlights the need for thorough family histories and presents challenges for genetic counseling.
Article Abstract
Due to novel gene therapy opportunities, genetic screening is no longer restricted to familial cases of ALS (FALS) cases but also aplies to the sporadic populations (SALS). Screening of four main genes (C9orf72, SOD1, TARDBP and FUS) identified the causes in 15% of Amyotrophic Lateral Sclerosis (ALS) patients (two third of the familial cases and 8% of the sporadic ones) but their respective contribution to ALS phenotype varies according the age of disease onset. The genetic overlap between ALS and other diseases is expanding and includes frontotemporal dementia, Paget's Disease of Bone, myopathy for adult cases, HSP and CMT for young cases highlighing the importance of retrieving the exhaustive familial history for each indivdual with ALS. Incomplete disease penetrance, diversity of the possible phenotypes, as well as the lack of confidence concerning the pathogenicity of most identified variants and/or possible oligogenic inheritance are burdens of ALS genetic counseling to be delivered to patients and at risk individuals. The multitude of rare ALS genetic causes identifed seems to converge to similar cellular pathways leading to inapropriate response to stress emphacising new potential therapeutic options for the disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neurol.2021.01.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Association between cardiometabolic diseases and the risk and progression of motor neuron diseases in Sweden: a population-based case-control study.
Lancet Reg Health Eur
February 2025
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Background: The evidence on the link between cardiometabolic diseases (CMDs) and motor neuron diseases (MNDs) remains inconsistent. We aimed to determine whether there is an association of CMDs, namely, any cardiovascular disease, cardiac arrhythmia, heart failure, thromboembolic disease, hypertension, cerebrovascular disease, ischemic heart disease, diabetes mellitus type 2, and hypercholesterolemia with the risk and progression of MNDs.
Methods: We included 1463 MND patients (amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive spinal muscular atrophy (PSMA), and unspecified MND) diagnosed from January 1, 2015, to July 1, 2023, in Sweden according to the Swedish Motor Neuron Disease Quality Registry (i.
Pharmacogenomics for neurodegenerative disorders - a focused review.
Front Pharmacol
December 2024
Department of Anaesthesia Technology, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University (KKU), Abha, Saudi Arabia.
Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by the progressive degeneration of neuronal structure and function, leading to severe cognitive and motor impairments. These conditions present significant challenges to healthcare systems, and traditional treatments often fail to account for genetic variability among patients, resulting in inconsistent therapeutic outcomes. Pharmacogenomics aims to tailor medical treatments based on an individual's genetic profile, thereby improving therapeutic efficacy and reducing adverse effects.
View Article and Find Full Text PDFRegulation of physiological and pathological condensates by molecular chaperones.
FEBS J
January 2025
Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Biomolecular condensates are dynamic membraneless compartments that regulate a myriad of cellular functions. A particular type of physiological condensate called stress granules (SGs) has gained increasing interest due to its role in the cellular stress response and various diseases. SGs, composed of several hundred RNA-binding proteins, form transiently in response to stress to protect mRNAs from translation and disassemble when the stress subsides.
View Article and Find Full Text PDFGain-of-function ANXA11 mutation cause late-onset ALS with aberrant protein aggregation, neuroinflammation and autophagy impairment.
Acta Neuropathol Commun
January 2025
Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College (PUMC) and Chinese Academy of Medical Science (CAMS), Beijing, China.
Mutations in the ANXA11 gene, encoding an RNA-binding protein, have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but the underlying in vivo mechanisms remain unclear. This study examines the clinical features of ALS patients harboring the ANXA11 hotspot mutation p.P36R, characterized by late-onset motor neuron disease and occasional multi-system involvement.
View Article and Find Full Text PDFA Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.
CNS Neurosci Ther
January 2025
Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China.
Background: Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double-stranded RNA (dsRNA) molecules into inosine in a process known as A-to-I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.
Results: In recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!