ArticleAnnals of neurology2015
Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants in known amyotrophic lateral sclerosis genes.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
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Who cites it
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 215 citations in OpenAlex.
- Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers: A Systematic Review and Meta-analysis.JAMA neurology · 2020Pooled it
- Insertion or deletion variants in TAF15 exon 15 are genetic factors impacting the prognosis of amyotrophic lateral sclerosis in a Japanese cohort.European journal of human genetics : EJHG · 2026Article
- TAF15 amyloids propagate via defined motifs in a prion-like fashion.Nature communications · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Wild-typemedRxiv : the preprint server for health sciences · 2026Article
- Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view.Frontiers in neurology · 2026Review
- Clinical and genetic determinants of survival in amyotrophic lateral sclerosis patients from North India.Brain communications · 2026Article
- A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.Communications biology · 2025Article
- The genetic architecture of primary lateral sclerosis in a cohort of Italian patients.Journal of neurology · 2025Article
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Article
- Protein Structure-based FUS Mutational Subtypes Are Associated With Protein Mislocalization in Amyotrophic Lateral Sclerosis Patients.Molecular neurobiology · 2025Article
- Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications.Journal of neurology, neurosurgery, and psychiatry · 2025Article
- Unravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration.Open biology · 2025Article
- Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.Life (Basel, Switzerland) · 2025Review
- Multiomics Approach Reveal Novel Insights in FUS Driven Juvenile Amyotrophic Lateral Sclerosis: A Family Quartet Analysis.Annals of neurosciences · 2025Article
- Role of lipocalin-2 in amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2025Review
- Combined impact ofFrontiers in neurology · 2025Article
- Engine breakdown of lysosomes and related organelles and the resulting physiology.Frontiers in cell and developmental biology · 2025Review
- Clinical features and progress in diagnosis and treatment of amyotrophic lateral sclerosis.Annals of medicine · 2024Review
62 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveTo define the genetic landscape of amyotrophic lateral sclerosis (ALS) and assess the contribution of possible oligogenic inheritance, we aimed to comprehensively sequence 17 known ALS genes in 391 ALS patients from the United States.
methodsTargeted pooled-sample sequencing was used to identify variants in 17 ALS genes. Fragment size analysis was used to define ATXN2 and C9ORF72 expansion sizes. Genotype-phenotype correlations were made with individual variants and total burden of variants. Rare variant associations for risk of ALS were investigated at both the single variant and gene level.
resultsA total of 64.3% of familial and 27.8% of sporadic subjects carried potentially pathogenic novel or rare coding variants identified by sequencing or an expanded repeat in C9ORF72 or ATXN2; 3.8% of subjects had variants in >1 ALS gene, and these individuals had disease onset 10 years earlier (p = 0.0046) than subjects with variants in a single gene. The number of potentially pathogenic coding variants did not influence disease duration or site of onset.
interpretationRare and potentially pathogenic variants in known ALS genes are present in >25% of apparently sporadic and 64% of familial patients, significantly higher than previous reports using less comprehensive sequencing approaches. A significant number of subjects carried variants in >1 gene, which influenced the age of symptom onset and supports oligogenic inheritance as relevant to disease pathogenesis.
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