ArticleBrain : a journal of neurology2018
Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.
Article in Brain : a journal 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.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Significant differences in phenotype and age of onset in an SPG4 family caused by whole SPAST deletion combined with a hemizygous S44L modifier.Neurogenetics · 2026Article
- A GJA1 Variant Triggers Earlier SPG4 Onset by Destabilizing Deubiquitinase VCPIP1 to Lower SPASTIN Levels.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Copy Number Variations in Hereditary Spastic Paraplegia-Related Genes: Evaluation of an Iranian Hereditary Spastic Paraplegia Cohort and Literature Review.Molecular syndromology · 2023Article
- Mechanisms underlying phenotypic variation in neurogenetic disorders.Nature reviews. Neurology · 2023Review
- Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges.Archives of pharmacal research · 2023Review
- PLP1 gene mutations cause spastic paraplegia type 2 in three families.Annals of clinical and translational neurology · 2023Article
- Modeling gain-of-function and loss-of-function components of SPAST-based hereditary spastic paraplegia using transgenic mice.Human molecular genetics · 2022Article
- A novel truncating variant ofFrontiers in neurology · 2022Article
- The Role of Spastin in Axon Biology.Frontiers in cell and developmental biology · 2022Review
- A novel mutation in theFrontiers in genetics · 2022Article
- Molecular and cellular mechanisms of spastin in neural development and disease (Review).International journal of molecular medicine · 2021Review
- Therapeutic Strategies for MutantBrain sciences · 2021Review
- The investigation of genetic and clinical features in patients with hereditary spastic paraplegia in central-Southern China.Molecular genetics & genomic medicine · 2021Article
- Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview.Frontiers in molecular biosciences · 2021Review
- Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia.Annals of clinical and translational neurology · 2020Article
- The complex activities of the SET1/MLL complex core subunits in development and disease.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- Genetic and Clinical Profile of Chinese Patients with Autosomal Dominant Spastic Paraplegia.Molecular diagnosis & therapy · 2019Article
- Hereditary spastic paraplegia: gain-of-function mechanisms revealed by new transgenic mouse.Human molecular genetics · 2019Article
- Spastin MIT Domain Disease-Associated Mutations Disrupt Lysosomal Function.Frontiers in neuroscience · 2019Article
- Perspectives on the Genomics of HSP Beyond Mendelian Inheritance.Frontiers in neurology · 2018Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 4 countries.
Funding
Abstract
Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.
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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.