ArticleAnnals of neurology2018
Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.
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 115 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
115 citing papers in PubMed, 163 citations in OpenAlex.
- Consensus recommendations for next-generation sequencing-based genetic testing in Rare Neurological diseases.European journal of human genetics : EJHG · 2026Article
- Gene set mediation analysis in high-dimensional epigenetic studies.Briefings in bioinformatics · 2026Article
- Mechanisms and Therapeutic Potential of Targeting Mitophagy in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- How Early Should I Refer My Patient? The Benefits of a Quick Ophthalmic Referral in Spinocerebellar Ataxias, a Case Series and Literature Review.Brain sciences · 2026Article
- Adult-Onset SCAR4 with a 30-Year Slowly Progressive Course: First Combined Assessment with FDG-PET and Brain Perfusion SPECT.Cerebellum (London, England) · 2026Review
- Four subtypes of disease-causing missense mutations underlie pathogenic protein interactions in neurodegenerative VPS13A disease.The Journal of clinical investigation · 2026Article
- Expanding the genetic and clinical landscapes of hereditary spastic paraplegia (HSP): a cohort study of 103 families.Orphanet journal of rare diseases · 2026Article
- Hoi1 targets BLTP2 to ER-PM contact sites to regulate lipid homeostasis.The Journal of cell biology · 2026Article
- Article
- The molecular mechanism of lipid uptake by membrane-anchored bridge-like lipid transfer proteins.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- The conserved outer mitochondrial membrane protein Mtch regulates mitophagy during Drosophila intestinal development.PLoS biology · 2026Article
- Proceedings of the 12Tremor and other hyperkinetic movements (New York, N.Y.) · 2026Article
- VPS13B recruits lipid vesicles to promote mitochondrial fission and quality control.Nature communications · 2025Article
- VPS13D-Related Disorders: Description of New Variant and Phenotypic Spectrum Based on Age of Onset.Cerebellum (London, England) · 2025Article
- Neuronal VPS13D loss drives microglial activation.Nature structural & molecular biology · 2025Article
- Microglia promote inflammatory cell death upon neuronal mitochondrial impairment during neurodegeneration.Nature structural & molecular biology · 2025Article
- Wings of Discovery: UsingCells · 2025Review
- Impaired hematopoiesis and embryonic lethality at midgestation of mice lacking both lipid transfer proteins VPS13A and VPS13C.PLoS biology · 2025Article
- POLR3A rare variants in a patient with intellectual disability, ataxic gait and cortical malformations: a case-report.Italian journal of pediatrics · 2025Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveTo identify novel causes of recessive ataxias, including spinocerebellar ataxia with saccadic intrusions, spastic ataxias, and spastic paraplegia.
methodsIn an international collaboration, we independently performed exome sequencing in 7 families with recessive ataxia and/or spastic paraplegia. To evaluate the role of VPS13D mutations, we evaluated a Drosophila knockout model and investigated mitochondrial function in patient-derived fibroblast cultures.
resultsExome sequencing identified compound heterozygous mutations in VPS13D on chromosome 1p36 in all 7 families. This included a large family with 5 affected siblings with spinocerebellar ataxia with saccadic intrusions (SCASI), or spinocerebellar ataxia, recessive, type 4 (SCAR4). Linkage to chromosome 1p36 was found in this family with a logarithm of odds score of 3.1. The phenotypic spectrum in our 12 patients was broad. Although most presented with ataxia, additional or predominant spasticity was present in 5 patients. Disease onset ranged from infancy to 39 years, and symptoms were slowly progressive and included loss of independent ambulation in 5. All but 2 patients carried a loss-of-function (nonsense or splice site) mutation on one and a missense mutation on the other allele. Knockdown or removal of Vps13D in Drosophila neurons led to changes in mitochondrial morphology and impairment in mitochondrial distribution along axons. Patient fibroblasts showed altered morphology and functionality including reduced energy production.
interpretationOur study demonstrates that compound heterozygous mutations in VPS13D cause movement disorders along the ataxia-spasticity spectrum, making VPS13D the fourth VPS13 paralog involved in neurological disorders. Ann Neurol 2018.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.