ArticleGenes2020
High-Throughput Genetic Testing in ALS: The Challenging Path of Variant Classification Considering the ACMG Guidelines.
Article in Genes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Contrasting clinical trajectories in two ALS patients with rare FUS variants: implications for variant interpretation, penetrance, and trial readiness.Neurogenetics · 2026Article
- Phenotypic Characterization of ALS-Causing SOD1 Mutations Affecting Polypeptide Length.Human mutation · 2025Article
- Characterizing proteomic and transcriptomic features of missense variants in amyotrophic lateral sclerosis genes.Brain : a journal of neurology · 2023Article
- Evidence-based consensus guidelines for ALS genetic testing and counseling.Annals of clinical and translational neurology · 2023Article
- Genetic variability in sporadic amyotrophic lateral sclerosis.Brain : a journal of neurology · 2023Article
- Advantages of routine next-generation sequencing over standard genetic testing in the amyotrophic lateral sclerosis clinic.European journal of neurology · 2023Article
- Evaluating the Utility of REVEL and CADD for Interpreting Variants in Amyotrophic Lateral Sclerosis Genes.Human mutation · 2023Article
- Article
- Revealing the Mutational Spectrum in Southern Africans With Amyotrophic Lateral Sclerosis.Neurology. Genetics · 2022Article
- Amyotrophic Lateral Sclerosis Genetic Access Program: Paving the Way for Genetic Characterization of ALS in the Clinic.Neurology. Genetics · 2021Article
- Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2021Review
- Targeting S100A4 with niclosamide attenuates inflammatory and profibrotic pathways in models of amyotrophic lateral sclerosis.Journal of neuroinflammation · 2021Article
- Unbiased Label-Free Quantitative Proteomics of Cells Expressing Amyotrophic Lateral Sclerosis (ALS) Mutations inFrontiers in molecular neuroscience · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of high-throughput sequencing technologies and screening of big patient cohorts with familial and sporadic amyotrophic lateral sclerosis (ALS) led to the identification of a significant number of genetic variants, which are sometimes difficult to interpret. The American College of Medical Genetics and Genomics (ACMG) provided guidelines to help molecular geneticists and pathologists to interpret variants found in laboratory testing. We assessed the application of the ACMG criteria to ALS-related variants, combining data from literature with our experience. We analyzed a cohort of 498 ALS patients using massive parallel sequencing of ALS-associated genes and identified 280 variants with a minor allele frequency < 1%. Examining all variants using the ACMG criteria, thus considering the type of variant, inheritance, familial segregation, and possible functional studies, we classified 20 variants as "pathogenic". In conclusion, ALS's genetic complexity, such as oligogenic inheritance, presence of genes acting as risk factors, and reduced penetrance, needs to be considered when interpreting variants. The goal of this work is to provide helpful suggestions to geneticists and clinicians dealing with ALS.
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