ArticleThe Journal of clinical investigation2024
Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Squamocin as the Principal Toxic Constituent ofInternational journal of molecular sciences · 2026Article
- Presynaptic Terminal Alterations in Concave and Convex Spinalis Muscles: A Pilot Exploratory Study in Advanced Scoliosis.Journal of clinical medicine · 2026Article
- CT-Derived Paraspinal Muscle Asymmetry Is Associated with Deformity Severity in Adolescent Idiopathic Scoliosis: A Quantitative CT Study.Journal of clinical medicine · 2026Article
- Genetic interaction betweenbioRxiv : the preprint server for biology · 2026Article
- Genetic interaction betweenResearch square · 2026Article
- Protocol for quantifying vertebral column morphology for the statistical analysis of scoliosis severity in zebrafish.STAR protocols · 2026Article
- LBX1 alters polyamine pathway in adolescent idiopathic scoliosis - a new therapeutic target to mitigate curve progression.Journal of orthopaedic translation · 2026Article
- The asymmetrical ROS-METTL3-ESR1 axis in paraspinal muscle progenitor cells determines the progression of adolescent idiopathic scoliosis.Experimental & molecular medicine · 2026Article
- Slc6a9 is distributed in glial cells and neurons across several nervous system regions, whereas Slc6a5 is more restricted to neurons in the caudal brain.BMC neuroscience · 2026Article
- Radiation-free 3D assessment of back height differences via three-dimensional depth sensing in adolescent idiopathic scoliosis: prospective, single-center, observational study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Observational
- Genome-wide association study identifiesPeerJ · 2026Article
- Integrating intrinsic musculoskeletal pathology and genetics: Recent advances in unravelling the causative factors of adolescent idiopathic scoliosis.Bone reports · 2025Review
- miRNA-130b-3p upregulation impairs osteogenic differentiation in AIS patients by inhibiting the IGF1/ERK pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Oxidative stress-induced intervertebral disc remodelling and elevated stiffness drive idiopathic scoliosis in preclinical models.Nature communications · 2025Article
- Butylated hydroxytoluene (BHT) induces zebrafish spinal cord defects and scoliosis by inhibiting the hedgehog pathway.Scientific reports · 2025Article
- The importance of imperfect pre-clinical models in adolescent idiopathic scoliosis.Disease models & mechanisms · 2025Review
- EPHA4 signaling dysregulation links abnormal locomotion and the development of idiopathic scoliosis.eLife · 2025Article
- C-mannosyltransferase DPY19L1L-mediated Reissner Fiber formation is critical for zebrafish (Science advances · 2025Article
- The Neurogenic Abnormities of Paraspinal Muscles Lead to Asymmetry of Fibre Types in Adolescent Idiopathic Scoliosis.Journal of cellular and molecular medicine · 2025Article
- Toxic endpoints or ubiquitous expression?Toxicology research · 2025Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.
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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 Socratic graph.