ArticleAmerican journal of human genetics2016
Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes.Clinical pharmacology and therapeutics · 2019Pooled it
- AGRN-, LRP4-, MUSK-Related CMS: Clinical, Neurophysiological, Morphological, Genetic and Pathological Mechanisms.Muscle & nerve · 2026Review
- Review of 40 genes causing congenital myasthenic syndromes.Journal of human genetics · 2025Review
- Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1.Cell discovery · 2024Article
- Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.Brain : a journal of neurology · 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
- 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
- The Importance of Early Treatment of Inherited Neuromuscular Conditions.Journal of neuromuscular diseases · 2024Review
- 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
- Neuromuscular junction involvement in inherited motor neuropathies: genetic heterogeneity and effect of oral salbutamol treatment.Journal of neurology · 2023Article
- Vocal Cord Paralysis and Feeding Difficulties as Early Diagnostic Clues of Congenital Myasthenic Syndrome with Neonatal Onset: A Case Report and Review of Literature.Journal of personalized medicine · 2023Review
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models.Journal of neuromuscular diseases · 2023Review
- Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation.Frontiers in human neuroscience · 2023Article
- Overexpression of mTOR in Leukocytes from ALS8 Patients.Current neuropharmacology · 2023Article
- Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression.Clinical epigenetics · 2022Article
- Phenotypical and Myopathological Consequences of Compound Heterozygous Missense and Nonsense Variants inCells · 2021Article
Corrections and comments
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Authors and funding
42 authors at 12 institutions in 4 countries.
Funding
Abstract
The neuromuscular junction (NMJ) is one of the best-studied cholinergic synapses. Inherited defects of peripheral neurotransmission result in congenital myasthenic syndromes (CMSs), a clinically and genetically heterogeneous group of rare diseases with fluctuating fatigable muscle weakness as the clinical hallmark. Whole-exome sequencing and Sanger sequencing in six unrelated families identified compound heterozygous and homozygous mutations in SLC5A7 encoding the presynaptic sodium-dependent high-affinity choline transporter 1 (CHT), which is known to be mutated in one dominant form of distal motor neuronopathy (DHMN7A). We identified 11 recessive mutations in SLC5A7 that were associated with a spectrum of severe muscle weakness ranging from a lethal antenatal form of arthrogryposis and severe hypotonia to a neonatal form of CMS with episodic apnea and a favorable prognosis when well managed at the clinical level. As expected given the critical role of CHT for multisystemic cholinergic neurotransmission, autonomic dysfunctions were reported in the antenatal form and cognitive impairment was noticed in half of the persons with the neonatal form. The missense mutations induced a near complete loss of function of CHT activity in cell models. At the human NMJ, a delay in synaptic maturation and an altered maintenance were observed in the antenatal and neonatal forms, respectively. Increased synaptic expression of butyrylcholinesterase was also observed, exposing the dysfunction of cholinergic metabolism when CHT is deficient in vivo. This work broadens the clinical spectrum of human diseases resulting from reduced CHT activity and highlights the complexity of cholinergic metabolism at the synapse.
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