ArticleHuman molecular genetics2015
Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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84 citing papers in PubMed, 138 citations in OpenAlex.
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- Structurally exclusive Teneurin complexes orchestrate divergent programs in early cortical development.Nature communications · 2026Article
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- At the extreme limits of L-DOPA therapy: probable dopamine dysregulation and psychiatric complications in Parkinson's disease.BMJ neurology open · 2026Article
- Spatial transcriptomics reveal heterogeneous cell‒cell interactions among brain regions in cuprizone model consistent with multiple sclerosis lesions.Frontiers in bioinformatics · 2026Article
- Synaptic Cell Adhesion: A Structural Perspective.Advances in neurobiology · 2026Review
- Transcript Imbalance from TENM4 Exon Skipping: Effects on Epilepsy and Genetic Pleiotropy.Molecular neurobiology · 2025Article
- Epigenetic Changes Associated with the Progression of Prion Disease in Syrian Hamsters (Mesocricetus auratus).Research square · 2025Article
- Loss-of-function variations in solute carrier family 38 member 6 are associated with essential tremor.Signal transduction and targeted therapy · 2025Article
- Axonal pathology differentially affects human Purkinje cell subpopulations in the essential tremor cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A heterozygous variation of PINK1 is potentially associated with essential tremor in a Chinese family.Neurogenetics · 2025Article
- Genetic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.Genes, brain, and behavior · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Axonal pathology differentially affects human Purkinje cell subtypes in the essential tremor cerebellum.bioRxiv : the preprint server for biology · 2025Article
- Tremor in the Age of Omics: An Overview of the Transcriptomic Landscape of Essential Tremor.Cerebellum (London, England) · 2025Review
- Article
- Fetal brain response to maternal inflammation requires microglia.Development (Cambridge, England) · 2024Article
- Cartography of teneurin and latrophilin expression reveals spatiotemporal axis heterogeneity in the mouse hippocampus during development.PLoS biology · 2024Article
24 more citing papers are in PubMed but not listed here.
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25 authors at 14 institutions in 4 countries.
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Abstract
Essential tremor (ET) is a common movement disorder with an estimated prevalence of 5% of the population aged over 65 years. In spite of intensive efforts, the genetic architecture of ET remains unknown. We used a combination of whole-exome sequencing and targeted resequencing in three ET families. In vitro and in vivo experiments in oligodendrocyte precursor cells and zebrafish were performed to test our findings. Whole-exome sequencing revealed a missense mutation in TENM4 segregating in an autosomal-dominant fashion in an ET family. Subsequent targeted resequencing of TENM4 led to the discovery of two novel missense mutations. Not only did these two mutations segregate with ET in two additional families, but we also observed significant over transmission of pathogenic TENM4 alleles across the three families. Consistent with a dominant mode of inheritance, in vitro analysis in oligodendrocyte precursor cells showed that mutant proteins mislocalize. Finally, expression of human mRNA harboring any of three patient mutations in zebrafish embryos induced defects in axon guidance, confirming a dominant-negative mode of action for these mutations. Our genetic and functional data, which is corroborated by the existence of a Tenm4 knockout mouse displaying an ET phenotype, implicates TENM4 in ET. Together with previous studies of TENM4 in model organisms, our studies intimate that processes regulating myelination in the central nervous system and axon guidance might be significant contributors to the genetic burden of this disorder.
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