{"doi":"10.1172/jci168783","title":"Impaired glycine neurotransmission causes adolescent idiopathic scoliosis","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.","journal":"Journal of Clinical Investigation","year":2023,"id":325218,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":262718,"name":"Ming Yue","orcid":"0000-0002-4052-818X","position":1,"is_corresponding":false},{"id":1042732,"name":"Jason Pui Yin Cheung","orcid":"0000-0002-7052-0875","position":2,"is_corresponding":false},{"id":1042733,"name":"Prudence Wing Hang Cheung","orcid":"0000-0002-3213-7373","position":3,"is_corresponding":false},{"id":1042734,"name":"Yanhui Fan","orcid":"0000-0001-9677-3777","position":4,"is_corresponding":false},{"id":1043394,"name":"Meicheng Wu","orcid":null,"position":5,"is_corresponding":false},{"id":607015,"name":"Xiaojun Wang","orcid":"0000-0002-6802-2623","position":6,"is_corresponding":false},{"id":475647,"name":"Sen Zhao","orcid":"0000-0001-9418-4231","position":7,"is_corresponding":false},{"id":316086,"name":"Anas M. Khanshour","orcid":null,"position":8,"is_corresponding":false},{"id":314823,"name":"Jonathan J. Rios","orcid":"0000-0002-0969-2184","position":9,"is_corresponding":false},{"id":227647,"name":"Zheyi Chen","orcid":"0000-0002-6349-068X","position":10,"is_corresponding":false},{"id":756304,"name":"Xiwei Wang","orcid":"0000-0002-3970-1336","position":11,"is_corresponding":false},{"id":1042735,"name":"Wenwei Tu","orcid":"0000-0002-6801-8798","position":12,"is_corresponding":false},{"id":494302,"name":"Danny Chan","orcid":"0000-0003-3824-5778","position":13,"is_corresponding":false},{"id":1042736,"name":"Qiuju Yuan","orcid":"0000-0002-0558-9518","position":14,"is_corresponding":false},{"id":1042737,"name":"Dajiang Qin","orcid":"0009-0008-2792-3514","position":15,"is_corresponding":false},{"id":475652,"name":"Guixing Qiu","orcid":"0000-0002-4597-9350","position":16,"is_corresponding":false},{"id":640454,"name":"Zhihong Wu","orcid":"0000-0002-1902-4198","position":17,"is_corresponding":false},{"id":640455,"name":"Jianguo Zhang","orcid":"0000-0003-3129-5190","position":18,"is_corresponding":false},{"id":34093,"name":"Shiro Ikegawa","orcid":"0000-0003-0316-2147","position":19,"is_corresponding":false},{"id":465839,"name":"Nan Wu","orcid":"0000-0002-9429-2889","position":20,"is_corresponding":false},{"id":314819,"name":"Carol A. Wise","orcid":"0000-0002-6790-2194","position":21,"is_corresponding":false},{"id":589791,"name":"Yong Hu","orcid":"0000-0003-0305-5616","position":22,"is_corresponding":false},{"id":1042738,"name":"K.D.K. Luk","orcid":"0000-0003-0547-8890","position":23,"is_corresponding":false},{"id":1042739,"name":"You‐Qiang Song","orcid":"0000-0001-9407-2256","position":24,"is_corresponding":false},{"id":494304,"name":"Bo Gao","orcid":"0000-0002-8684-5199","position":25,"is_corresponding":false},{"id":1042731,"name":"Xiaolu Wang","orcid":"0009-0001-9085-192X","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:08:22.919783Z","pmid":"37962965","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}