ArticleAmerican journal of human genetics2012
Defective presynaptic choline transport underlies hereditary motor neuropathy.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes.Clinical pharmacology and therapeutics · 2019Pooled it
- Presynaptic Congenital Myasthenic Syndromes.Muscle & nerve · 2026Review
- Ketogenic Diet and Exercise Improve Peripheral Neuropathy in a Mouse Model of Metabolic Syndrome.Diabetes · 2026Article
- Evaluation of the Metabolomics Profile in Charcot-Marie-Tooth (CMT) Patients: Novel Potential Biomarkers.Metabolites · 2025Article
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1.Cell discovery · 2024Article
- Congenital myasthenic syndrome secondary to pathogenic variants in the SLC5A7 gene: report of two cases.BMC medical genomics · 2024Article
- Genetic analysis of a family affected by congenital myasthenic syndrome due to a Novel mutation in the SLC5A7 gene.BMC neurology · 2024Article
- Streamlined Full-Length Total RNA Sequencing of Paraformaldehyde-Fixed Brain Tissues.International journal of molecular sciences · 2024Article
- CircFBXW4 Suppresses Colorectal Cancer Progression by Regulating the MiR-338-5p/SLC5A7 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transport mechanism of presynaptic high-affinity choline uptake by CHT1.Nature structural & molecular biology · 2024Article
- Biallelic variation in the choline and ethanolamine transportermedRxiv : the preprint server for health sciences · 2024Article
- A new patient with congenital myasthenic syndrome type 20 due to compound heterozygous missense SLC5A7 variants suggests trends in genotype-phenotype correlation.Molecular genetics & genomic medicine · 2023Article
- Novel gene-intergenic fusion involving ubiquitin E3 ligase UBE3C causes distal hereditary motor neuropathy.Brain : a journal of neurology · 2023Article
- Early onset hereditary neuronopathies: an update on non-5q motor neuron diseases.Brain : a journal of neurology · 2023Review
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation.Frontiers in human neuroscience · 2023Article
- Evolution and developmental expression of the sodium-iodide symporter (Evolutionary applications · 2022Article
- Disrupted Choline Clearance and Sustained Acetylcholine ReleaseThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
The neuromuscular junction (NMJ) is a specialized synapse with a complex molecular architecture that provides for reliable transmission between the nerve terminal and muscle fiber. Using linkage analysis and whole-exome sequencing of DNA samples from subjects with distal hereditary motor neuropathy type VII, we identified a mutation in SLC5A7, which encodes the presynaptic choline transporter (CHT), a critical determinant of synaptic acetylcholine synthesis and release at the NMJ. This dominantly segregating SLC5A7 mutation truncates the encoded product just beyond the final transmembrane domain, eliminating cytosolic-C-terminus sequences known to regulate surface transporter trafficking. Choline-transport assays in both transfected cells and monocytes from affected individuals revealed significant reductions in hemicholinium-3-sensitive choline uptake, a finding consistent with a dominant-negative mode of action. The discovery of CHT dysfunction underlying motor neuropathy identifies a biological basis for this group of conditions and widens the spectrum of disorders that derive from impaired NMJ transmission. Our findings compel consideration of mutations in SLC5A7 or its functional partners in relation to unexplained motor neuronopathies.
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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.