ArticleBrain : a journal of neurology2020
Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration.
Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Ethanolamine as a potential biomarker and therapeutic target for depressive disorder.Molecular psychiatry · 2026Article
- CRISPR/Cas9-mediatedFrontiers in physiology · 2026Article
- Homeostatic response of phospholipid pathways to PCYT2 deficiency and impaired de Novo synthesis of phosphatidylethanolamine.Scientific reports · 2025Article
- A novelMolecular genetics and metabolism reports · 2025Article
- Glycerophospholipids: Roles in Cell Trafficking and Associated Inborn Errors.Journal of inherited metabolic disease · 2025Review
- Gene therapy ameliorates bowel dysmotility and enteric neuron degeneration and extends survival in lysosomal storage disorder mouse models.Science translational medicine · 2025Article
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.Genes · 2024Article
- Biallelic variation in the choline and ethanolamine transportermedRxiv : the preprint server for health sciences · 2024Article
- Polymorphisms in the choline transporter SLC44A1 are associated with reduced cognitive performance in normotypic but not prenatal alcohol-exposed children.The American journal of clinical nutrition · 2024Article
- Choline metabolism underpins macrophage IL-4 polarization and RELMα up-regulation in helminth infection.PLoS pathogens · 2023Article
- The Efficacy of Whole Genome Sequencing and RNA-Seq in the Diagnosis of Whole Exome Sequencing Negative Patients with Complex Neurological Phenotypes.Journal of pediatric genetics · 2023Article
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- Bilayer Forming Phospholipids as Targets for Cancer Therapy.International journal of molecular sciences · 2022Review
- Phosphatidylethanolamine homeostasis under conditions of impaired CDP-ethanolamine pathway or phosphatidylserine decarboxylation.Frontiers in nutrition · 2022Review
- Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: an exploratory study of oral choline supplementation.The American journal of clinical nutrition · 2021Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
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Corrections and comments
- Erratum issuedErratum.2020
Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding choline transporter-like protein 1. Clinical features included progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrated cerebellar atrophy and leukoencephalopathy. Moreover, low signal intensity in globus pallidus with hyperintensive streaking and low signal intensity in substantia nigra were seen in two individuals. The Asp517Metfs*19 and Ser126Metfs*8 fibroblasts were structurally and functionally indistinguishable. The most prominent ultrastructural changes of the mutant fibroblasts were reduced presence of free ribosomes, the appearance of elongated endoplasmic reticulum and strikingly increased number of mitochondria and small vesicles. When chronically treated with choline, those characteristics disappeared and mutant ultrastructure resembled healthy control cells. Functional analysis revealed diminished choline transport yet the membrane phosphatidylcholine content remained unchanged. As part of the mechanism to preserve choline and phosphatidylcholine, choline transporter deficiency was implicated in impaired membrane homeostasis of other phospholipids. Choline treatments could restore the membrane lipids, repair cellular organelles and protect mutant cells from acute iron overload. In conclusion, we describe a novel childhood-onset neurometabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.
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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.