ArticleGenome research2011
Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis.
Article in Genome research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.
- Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review.Journal of neurology · 2022Pooled it
- KIF1A-associated neurological disorders: therapeutic opportunities and challenges.European journal of human genetics : EJHG · 2026Review
- The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.Journal of neurochemistry · 2026Review
- Dorsolateral Cervical Cord T2 Hyperintensity in KIF1C-Related Disease (Spastic Paraplegia 58): Two Long-Duration Cases.Annals of clinical and translational neurology · 2026Article
- Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A.Biomolecules · 2025Article
- Review of the Genetic Spectrum of Hereditary Spastic Paraplegias in the Middle East and North Africa Regions.Neurology. Genetics · 2025Review
- Engine breakdown of lysosomes and related organelles and the resulting physiology.Frontiers in cell and developmental biology · 2025Review
- Article
- Genotype-phenotype correlations in 18 European patients with heterozygousFrontiers in medicine · 2025Article
- Case Report: Hereditary spastic paraplegia associated with monoallelic variant in the motor domain of KIF1A.Frontiers in human neuroscience · 2025Article
- Ophthalmic Findings in the KIF1A-Associated Neurologic Disorder (KAND).American journal of ophthalmology · 2024Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
- Cryo-EM unveils kinesin KIF1A's processivity mechanism and the impact of its pathogenic variant P305L.Nature communications · 2024Article
- Long-term Observation of a Japanese Patient with a Multiple-system Neurodegenerative Disorder with a Uniallelic de novo Missense Variant in KIF1A.Internal medicine (Tokyo, Japan) · 2023Article
- Article
- KIF1A-Associated Neurological Disorder: An Overview of a Rare Mutational Disease.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Illustration of a rare case of hereditary spastic paraplegia type 30 associated with a missense variant in the non-motor domain of KIF1A.Journal of neurology · 2022Article
- Single-Molecule Studies on the Motion and Force Generation of the Kinesin-3 Motor KIF1A.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Vesicular dysfunction and pathways to neurodegeneration.Essays in biochemistry · 2021Article
- Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias.iScience · 2021Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Whole exome sequencing has become a pivotal methodology for rapid and cost-effective detection of pathogenic variations in Mendelian disorders. A major challenge of this approach is determining the causative mutation from a substantial number of bystander variations that do not play any role in the disease etiology. Current strategies to analyze variations have mainly relied on genetic and functional arguments such as mode of inheritance, conservation, and loss of function prediction. Here, we demonstrate that disease-network analysis provides an additional layer of information to stratify variations even in the presence of incomplete sequencing coverage, a known limitation of exome sequencing. We studied a case of Hereditary Spastic Paraparesis (HSP) in a single inbred Palestinian family. HSP is a group of neuropathological disorders that are characterized by abnormal gait and spasticity of the lower limbs. Forty-five loci have been associated with HSP and lesions in 20 genes have been documented to induce the disorder. We used whole exome sequencing and homozygosity mapping to create a list of possible candidates. After exhausting the genetic and functional arguments, we stratified the remaining candidates according to their similarity to the previously known disease genes. Our analysis implicated the causative mutation in the motor domain of KIF1A, a gene that has not yet associated with HSP, which functions in anterograde axonal transportation. Our strategy can be useful for a large class of disorders that are characterized by locus heterogeneity, particularly when studying disorders in single families.
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