دورية أكاديمية
أعرض في EDS

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.

التفاصيل البيبلوغرافية
العنوان: Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.
المؤلفون: Wang X; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.; School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China.; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Yue M; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Cheung JPY; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.; Department of Orthopaedics and Traumatology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China., Cheung PWH; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Fan Y; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Wu M; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Wang X; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Zhao S; Department of Orthopaedic Surgery, Department of Medical Research Center, Key Laboratory of Big Data for Spinal Deformities, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital (PUMCH) and Chinese Academy of Medical Sciences, Beijing, China., Khanshour AM; Center for Pediatric Bone Biology and Translational Research, Scottish Rite for Children (SRC), Dallas, Texas, USA., Rios JJ; Center for Pediatric Bone Biology and Translational Research, Scottish Rite for Children (SRC), Dallas, Texas, USA.; Eugene McDermott Center for Human Growth and Development, Departments of Orthopaedic Surgery and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Chen Z; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Wang X; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Tu W; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Chan D; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Yuan Q; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Tai Po, Hong Kong, China., Qin D; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Tai Po, Hong Kong, China., Qiu G; Department of Orthopaedic Surgery, Department of Medical Research Center, Key Laboratory of Big Data for Spinal Deformities, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital (PUMCH) and Chinese Academy of Medical Sciences, Beijing, China., Wu Z; Department of Orthopaedic Surgery, Department of Medical Research Center, Key Laboratory of Big Data for Spinal Deformities, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital (PUMCH) and Chinese Academy of Medical Sciences, Beijing, China., Zhang TJ; Department of Orthopaedic Surgery, Department of Medical Research Center, Key Laboratory of Big Data for Spinal Deformities, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital (PUMCH) and Chinese Academy of Medical Sciences, Beijing, China., Ikegawa S; Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan., Wu N; Department of Orthopaedic Surgery, Department of Medical Research Center, Key Laboratory of Big Data for Spinal Deformities, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital (PUMCH) and Chinese Academy of Medical Sciences, Beijing, China., Wise CA; Center for Pediatric Bone Biology and Translational Research, Scottish Rite for Children (SRC), Dallas, Texas, USA.; Eugene McDermott Center for Human Growth and Development, Departments of Orthopaedic Surgery and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Hu Y; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.; Department of Orthopaedics and Traumatology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China., Luk KDK; Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China., Song YQ; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.; Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.; State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Pokfulam, Hong Kong, China., Gao B; School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China.; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.; Department of Orthopaedics and Traumatology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.; Centre for Translational Stem Cell Biology, Tai Po, Hong Kong, China.; Key Laboratory of Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China.
المصدر: The Journal of clinical investigation [J Clin Invest] 2024 Jan 16; Vol. 134 (2). Date of Electronic Publication: 2024 Jan 16.
نوع المنشور: Multicenter Study; Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Scoliosis*/genetics , Scoliosis*/diagnosis , Scoliosis*/surgery, Animals ; Humans ; Adolescent ; Glycine/genetics ; Zebrafish ; Synaptic Transmission
مستخلص: 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.
References: J Bone Joint Surg Am. 1981 Jun;63(5):702-12. (PMID: 6453874)
J Pharmacol Sci. 2012;118(2):145-8. (PMID: 22293292)
Hum Mol Genet. 2011 Apr 1;20(7):1456-66. (PMID: 21216876)
Exp Brain Res. 1971 Jun 29;12(5):547-65. (PMID: 5093729)
Nat Commun. 2019 Mar 5;10(1):1060. (PMID: 30837465)
JAMA. 2003 Feb 5;289(5):559-67. (PMID: 12578488)
Nat Commun. 2018 Oct 9;9(1):4171. (PMID: 30301978)
Trends Biochem Sci. 2005 Jun;30(6):325-33. (PMID: 15950877)
J Biol Chem. 2009 Jul 17;284(29):19482-92. (PMID: 19473961)
PLoS One. 2015 Sep 29;10(9):e0138897. (PMID: 26418248)
Cell Rep. 2021 Nov 16;37(7):110017. (PMID: 34788621)
Spine (Phila Pa 1976). 1986 Oct;11(8):773-6. (PMID: 3810290)
Hum Mutat. 2021 Apr;42(4):392-407. (PMID: 33382518)
Neuron. 2002 May 16;34(4):535-49. (PMID: 12062038)
Trends Genet. 2017 Mar;33(3):183-196. (PMID: 28174019)
Am J Hum Genet. 2016 Nov 3;99(5):1172-1180. (PMID: 27773429)
J Bone Joint Surg Br. 1968 Feb;50(1):24-30. (PMID: 5641594)
Nat Methods. 2014 Sep;11(9):941-50. (PMID: 25068736)
J Clin Invest. 2015 Mar 2;125(3):1124-8. (PMID: 25642776)
J Child Orthop. 2012 Jul;6(3):199-203. (PMID: 23814620)
Dev Cell. 2015 Feb 23;32(4):408-22. (PMID: 25710528)
Neuron. 2003 Nov 13;40(4):785-96. (PMID: 14622582)
Hum Mol Genet. 2018 Nov 15;27(22):3986-3998. (PMID: 30395268)
Cell. 2019 Oct 3;179(2):355-372.e23. (PMID: 31564455)
Sci Rep. 2021 May 26;11(1):11026. (PMID: 34040021)
OMICS. 2012 May;16(5):284-7. (PMID: 22455463)
Front Mol Biosci. 2019 Sep 06;6:80. (PMID: 31555663)
Science. 2003 Mar 21;299(5614):1889-92. (PMID: 12649481)
Biochem J. 2008 Feb 1;409(3):669-81. (PMID: 17919119)
Nat Rev Dis Primers. 2015 Sep 24;1:15030. (PMID: 27188385)
Nat Commun. 2020 Jun 23;11(1):3168. (PMID: 32576830)
Am J Hum Genet. 2015 Aug 6;97(2):337-42. (PMID: 26211971)
J Neurochem. 2006 Jun;97(6):1600-10. (PMID: 16805771)
Mol Pharmacol. 2001 Dec;60(6):1414-20. (PMID: 11723250)
Lancet. 2008 May 3;371(9623):1527-37. (PMID: 18456103)
Nat Rev Neurosci. 2009 Jul;10(7):507-18. (PMID: 19543221)
Cell Res. 2020 Sep;30(9):717-731. (PMID: 32355288)
J Neurosci. 2005 Jul 13;25(28):6610-20. (PMID: 16014722)
J Cell Biol. 2014 Mar 17;204(6):869-79. (PMID: 24637321)
Nat Commun. 2015 Mar 18;6:6452. (PMID: 25784220)
J Emerg Med. 1990 May-Jun;8(3):321-5. (PMID: 2197324)
Eur Spine J. 2005 Mar;14(2):130-7. (PMID: 15368104)
J Electromyogr Kinesiol. 2022 Apr;63:102640. (PMID: 35219074)
Nat Rev Drug Discov. 2013 Nov;12(11):866-85. (PMID: 24172334)
J Neurophysiol. 2004 Oct;92(4):2003-9. (PMID: 15201312)
Am J Hum Genet. 2007 May;80(5):957-65. (PMID: 17436250)
Development. 2020 Oct 6;147(21):. (PMID: 33023886)
Nature. 2012 Aug 30;488(7413):642-6. (PMID: 22932389)
Cell Mol Life Sci. 2001 May;58(5-6):760-93. (PMID: 11437237)
Nat Methods. 2015 Oct;12(10):982-8. (PMID: 26322839)
J Bone Joint Surg Am. 1983 Apr;65(4):447-55. (PMID: 6833318)
Dev Cell. 2017 Aug 21;42(4):388-399.e3. (PMID: 28829946)
Dev Dyn. 1995 Jul;203(3):253-310. (PMID: 8589427)
Nucleic Acids Res. 2019 Jul 02;47(W1):W171-W174. (PMID: 31106371)
Med Eng Phys. 2010 Oct;32(8):840-8. (PMID: 20561810)
J Biol Chem. 2008 Apr 18;283(16):10978-91. (PMID: 18252709)
Nat Commun. 2015 Sep 22;6:8355. (PMID: 26394188)
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012. (PMID: 30445434)
N Engl J Med. 2016 Oct 6;375(14):1355-1364. (PMID: 27653382)
Am J Hum Genet. 2016 Dec 1;99(6):1406-1408. (PMID: 27912047)
J Clin Psychopharmacol. 1999 Dec;19(6):506-12. (PMID: 10587285)
Elife. 2020 Jan 29;9:. (PMID: 31995030)
Nat Rev Neurosci. 2016 Apr;17(4):224-38. (PMID: 26935168)
J Child Orthop. 2013 Feb;7(1):3-9. (PMID: 24432052)
Br J Dis Chest. 1986 Oct;80(4):360-9. (PMID: 3620323)
Curr Genomics. 2008 Mar;9(1):51-9. (PMID: 19424484)
Development. 2005 Oct;132(20):4471-81. (PMID: 16162647)
Nat Genet. 2011 Oct 23;43(12):1237-40. (PMID: 22019779)
Sci Adv. 2018 Dec 12;4(12):eaav1781. (PMID: 30547092)
Curr Biol. 2020 Jun 22;30(12):2353-2362.e3. (PMID: 32386529)
Cell Rep. 2020 Mar 3;30(9):3036-3050.e4. (PMID: 32130905)
Metabolism. 1977 May;26(5):517-24. (PMID: 850482)
Curr Biol. 2020 Mar 9;30(5):827-839.e4. (PMID: 32084399)
PLoS One. 2019 Mar 7;14(3):e0213269. (PMID: 30845169)
N Engl J Med. 2013 Feb 28;368(9):834-41. (PMID: 23445094)
Nat Commun. 2019 Aug 15;10(1):3685. (PMID: 31417091)
Nature. 2013 Aug 1;500(7460):85-8. (PMID: 23812590)
Nat Genet. 2013 Jun;45(6):676-9. (PMID: 23666238)
Nat Genet. 2018 Dec;50(12):1666-1673. (PMID: 30420648)
Front Neurol. 2013 Feb 08;3:183. (PMID: 23403923)
Science. 2016 Jun 10;352(6291):1341-4. (PMID: 27284198)
Neuron. 2002 May 16;34(4):551-62. (PMID: 12062039)
Handb Exp Pharmacol. 2006;(175):233-49. (PMID: 16722239)
Eur Spine J. 2000 Jun;9(3):178-84. (PMID: 10905433)
eNeuro. 2020 May 18;7(3):. (PMID: 32357958)
Science. 2004 Jun 4;304(5676):1509-13. (PMID: 15105459)
Hum Genet. 2016 Nov;135(11):1263-1268. (PMID: 27481395)
معلومات مُعتمدة: P01 HD084387 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Bone Biology; Bone disease; Genetic diseases; Genetics; Orthopedics
المشرفين على المادة: TE7660XO1C (Glycine)
تواريخ الأحداث: Date Created: 20231114 Date Completed: 20240117 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10786698
DOI: 10.1172/JCI168783
PMID: 37962965
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI168783