ArticleAnnals of neurology2018
CHCHD10 variants in amyotrophic lateral sclerosis: Where is the evidence?
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- PolyQ-expanded ataxin-3 is associated with mitochondrial alterations in Machado-Joseph disease.Disease models & mechanisms · 2026Article
- Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration.Amino acids · 2026Review
- Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolism.Acta neuropathologica communications · 2025Article
- Exploring Monogenic, Polygenic, and Epigenetic Models of Common Variable Immunodeficiency.Human mutation · 2025Review
- Skeletal muscle in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2023Review
- Neuroprotective Effect of Sonic Hedgehog Mediated PI3K/AKT Pathway in Amyotrophic Lateral Sclerosis Model Mice.Molecular neurobiology · 2022Article
- Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022Review
- Altered Mitochondrial Protein Homeostasis and Proteinopathies.Frontiers in molecular neuroscience · 2022Review
- Advances in the genetic classification of amyotrophic lateral sclerosis.Current opinion in neurology · 2021Review
- Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration.International journal of molecular sciences · 2021Review
- Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology.iScience · 2021Article
- [Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Mitochondrial Quality Control Strategies: Potential Therapeutic Targets for Neurodegenerative Diseases?Frontiers in neuroscience · 2021Review
- Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis.Cells · 2020Review
- Article
- The Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes.Life (Basel, Switzerland) · 2020Review
- Neuropathologic description ofNeurology. Genetics · 2020Article
- Multifaceted Genes in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia.Frontiers in neuroscience · 2020Review
- The project MinE databrowser: bringing large-scale whole-genome sequencing in ALS to researchers and the public.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2019Article
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Funding
Abstract
objectiveAfter the initial report of a CHCHD10 mutation in mitochondrial disease with features resembling amyotrophic lateral sclerosis (ALS), CHCHD10 mutations have been considered to be a frequent cause for ALS. However, the exact pathogenicity and clinical significance of these mutations remain unclear. Here, we aimed to determine the role of CHCHD10 mutations in ALS.
methodsWe analyzed 4,365 whole genome sequenced ALS patients and 1,832 controls from 7 different countries and examined all nonsynonymous single nucleotide variants in CHCHD10. These were tested for association with ALS, independently and in aggregate using several genetic burden tests (including sequence kernel association test [SKAT], optimal unified test [SKAT-O], and Firth logistic regression).
resultsWe identified 3 new variants in cases, but only 1 was ALS-specific. Also, 1 control-specific mutation was identified. There was no increased burden of rare coding mutations among ALS patients compared to controls (p = 0.86, p = 0.86, and p = 0.88 for SKAT, SKAT-O, and Firth, respectively). The few carriers with potential pathogenic CHCHD10 mutations exhibited a slowly progressive ALS-like phenotype with atypical features such as myopathy and deafness.
interpretationCHCHD10 mutations seem to be a far less prevalent cause of pure ALS than previously suggested, and instead appear related to more complex phenotypes. There appears to be insufficient evidence for the pathogenicity of most previously reported variants in pure ALS. This study shows that routine testing for CHCHD10 mutations in pure ALS is not recommended and illustrates the importance of sufficient genetic and functional evidence in establishing pathogenicity of genetic variants. Ann Neurol 2018;83:110-116.
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