{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:41:12Z","timestamp":1792788072714,"version":"4.5.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the National Natural Science Foundation of China","award":["82102527"],"award-info":[{"award-number":["82102527"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Natural Science Foundation of Hunan Province","award":["2022JJ30967"],"award-info":[{"award-number":["2022JJ30967"]}]},{"name":"the Natural Science Project of Changsha City","award":["kq2202117"],"award-info":[{"award-number":["kq2202117"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"DOI":"10.1186\/s12920-026-02422-6","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:28:04Z","timestamp":1783517284000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and growth features of developmental delay with macrocephaly caused by a novel TRIO variant affecting the second SH3 domain"],"prefix":"10.1186","volume":"19","author":[{"given":"Si-Yuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Yuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Chao","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"issue":"11","key":"2422_CR1","doi-asserted-by":"publisher","first-page":"5466","DOI":"10.1073\/pnas.93.11.5466","volume":"93","author":"A Debant","year":"1996","unstructured":"Debant A, Serra-Pages C, Seipel K, O\u2019Brien S, Tang M, Park SH, et al. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc Natl Acad Sci U S A. 1996;93(11):5466\u201371.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"2422_CR2","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.pneurobio.2011.04.011","volume":"94","author":"KF Tolias","year":"2011","unstructured":"Tolias KF, Duman JG, Um K. Control of synapse development and plasticity by Rho GTPase regulatory proteins. Prog Neurobiol. 2011;94(2):133\u201348.","journal-title":"Prog Neurobiol"},{"issue":"11","key":"2422_CR3","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1136\/jmedgenet-2016-103942","volume":"53","author":"RJ Pengelly","year":"2016","unstructured":"Pengelly RJ, Greville-Heygate S, Schmidt S, Seaby EG, Jabalameli MR, Mehta SG, et al. Mutations specific to the Rac-GEF domain of TRIO cause intellectual disability and microcephaly. J Med Genet. 2016;53(11):735\u201342.","journal-title":"J Med Genet"},{"issue":"5","key":"2422_CR4","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1093\/hmg\/ddv618","volume":"25","author":"W Ba","year":"2016","unstructured":"Ba W, Yan Y, Reijnders MR, Schuurs-Hoeijmakers JH, Feenstra I, Bongers EM, et al. TRIO loss of function is associated with mild intellectual disability and affects dendritic branching and synapse function. Hum Mol Genet. 2016;25(5):892\u2013902.","journal-title":"Hum Mol Genet"},{"issue":"20","key":"2422_CR5","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1056\/NEJMoa1206524","volume":"367","author":"J de Ligt","year":"2012","unstructured":"de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012;367(20):1921\u20139.","journal-title":"N Engl J Med"},{"issue":"7","key":"2422_CR6","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1002\/ajmg.a.63194","volume":"191","author":"G Gazdagh","year":"2023","unstructured":"Gazdagh G, Hunt D, Gonzalez AMC, Rodriguez MP, Chaudhry A, Madruga M, et al. Extending the phenotypes associated with TRIO gene variants in a cohort of 25 patients and review of the literature. Am J Med Genet A. 2023;191(7):1722\u201340.","journal-title":"Am J Med Genet A"},{"issue":"4","key":"2422_CR7","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/s41380-023-01963-x","volume":"28","author":"M Bonnet","year":"2023","unstructured":"Bonnet M, Roche F, Fagotto-Kaufmann C, Gazdagh G, Truong I, Comunale F, et al. Pathogenic TRIO variants associated with neurodevelopmental disorders perturb the molecular regulation of TRIO and axon pathfinding in vivo. Mol Psychiatry. 2023;28(4):1527\u201344.","journal-title":"Mol Psychiatry"},{"issue":"3","key":"2422_CR8","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.ajhg.2020.01.018","volume":"106","author":"S Barbosa","year":"2020","unstructured":"Barbosa S, Greville-Heygate S, Bonnet M, Godwin A, Fagotto-Kaufmann C, Kajava AV, et al. Opposite Modulation of RAC1 by Mutations in TRIO Is Associated with Distinct, Domain-Specific Neurodevelopmental Disorders. Am J Hum Genet. 2020;106(3):338\u201355.","journal-title":"Am J Hum Genet"},{"issue":"23","key":"2422_CR9","doi-asserted-by":"publisher","first-page":"4728","DOI":"10.1093\/hmg\/ddx355","volume":"26","author":"SM Katrancha","year":"2017","unstructured":"Katrancha SM, Wu Y, Zhu M, Eipper BA, Koleske AJ, Mains RE. Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP\/GTP exchange factor activity. Hum Mol Genet. 2017;26(23):4728\u201340.","journal-title":"Hum Mol Genet"},{"issue":"7","key":"2422_CR10","first-page":"663","volume":"36","author":"Growth Standard for Children Under 7 Years of Age","year":"2023","unstructured":"Growth Standard for Children Under 7 Years of Age. Biomed Environ Sci. 2023;36(7):663\u20134.","journal-title":"Biomed Environ Sci"},{"issue":"3","key":"2422_CR11","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/BF00913694","volume":"5","author":"RS Ball","year":"1977","unstructured":"Ball RS. The Gesell Developmental Schedules: Arnold Gesell (1880\u20131961). J Abnorm Child Psychol. 1977;5(3):233\u20139.","journal-title":"J Abnorm Child Psychol"},{"key":"2422_CR12","doi-asserted-by":"publisher","first-page":"1568643","DOI":"10.3389\/fneur.2025.1568643","volume":"16","author":"D Liu","year":"2025","unstructured":"Liu D, Duan M, Chen C, Xue J, Yue L. Efficacy analysis of comprehensive rehabilitation therapy based on the Gesell developmental schedules among infants with global developmental delay of different ages: a retrospective study. Front Neurol. 2025;16:1568643.","journal-title":"Front Neurol"},{"key":"2422_CR13","doi-asserted-by":"publisher","first-page":"781388","DOI":"10.3389\/fcell.2021.781388","volume":"9","author":"JY Jin","year":"2021","unstructured":"Jin JY, Wu PF, Luo FM, Guo BB, Zeng L, Fan LL, et al. GLIS Family Zinc Finger 1 was First Linked With Preaxial Polydactyly I in Humans by Stepwise Genetic Analysis. Front Cell Dev Biol. 2021;9:781388.","journal-title":"Front Cell Dev Biol"},{"issue":"5","key":"2422_CR14","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"issue":"12","key":"2422_CR15","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/j.ajhg.2022.10.013","volume":"109","author":"V Pejaver","year":"2022","unstructured":"Pejaver V, Byrne AB, Feng BJ, Pagel KA, Mooney SD, Karchin R, et al. Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3\/BP4 criteria. Am J Hum Genet. 2022;109(12):2163\u201377.","journal-title":"Am J Hum Genet"},{"issue":"5","key":"2422_CR16","doi-asserted-by":"publisher","first-page":"104405","DOI":"10.1016\/j.braindev.2025.104405","volume":"47","author":"T Hiraide","year":"2025","unstructured":"Hiraide T, Hayashi T, Yamoto K, Masunaga Y, Asahina M, Ogata T, et al. An atypical case of macrocephaly and severe intellectual disability associated with a missense variant in the guanine nucleotide exchange factor-1 domain of TRIO. Brain Dev. 2025;47(5):104405.","journal-title":"Brain Dev"},{"issue":"2","key":"2422_CR17","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/sj.onc.1201532","volume":"16","author":"JM Bellanger","year":"1998","unstructured":"Bellanger JM, Lazaro JB, Diriong S, Fernandez A, Lamb N, Debant A. The two guanine nucleotide exchange factor domains of Trio link the Rac1 and the RhoA pathways in vivo. Oncogene. 1998;16(2):147\u201352.","journal-title":"Oncogene"},{"issue":"9","key":"2422_CR18","doi-asserted-by":"publisher","first-page":"102361","DOI":"10.1016\/j.jbc.2022.102361","volume":"298","author":"JE Bircher","year":"2022","unstructured":"Bircher JE, Corcoran EE, Lam TT, Trnka MJ, Koleske AJ. Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. J Biol Chem. 2022;298(9):102361.","journal-title":"J Biol Chem"},{"issue":"12","key":"2422_CR19","doi-asserted-by":"publisher","first-page":"4232","DOI":"10.1093\/brain\/awac049","volume":"145","author":"S Banka","year":"2022","unstructured":"Banka S, Bennington A, Baker MJ, Rijckmans E, Clemente GD, Ansor NM, et al. Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology. Brain. 2022;145(12):4232\u201345.","journal-title":"Brain"},{"issue":"10","key":"2422_CR20","doi-asserted-by":"publisher","first-page":"3386","DOI":"10.1210\/en.2016-1691","volume":"158","author":"D Suzuki","year":"2017","unstructured":"Suzuki D, Bush JR, Bryce DM, Kamijo R, Beier F. Rac1 Dosage Is Crucial for Normal Endochondral Bone Growth. Endocrinology. 2017;158(10):3386\u201398.","journal-title":"Endocrinology"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-026-02422-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-026-02422-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-026-02422-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:02:05Z","timestamp":1790946125000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12920-026-02422-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2422"],"URL":"https:\/\/doi.org\/10.1186\/s12920-026-02422-6","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"25 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This research was approved by the Review Board of Xiangya Hospital of Central South University (202103427). This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent to participate has been obtained from all the participants and the parents\/legal guardians of minors.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent for publication of their personal or clinical details, along with any identifying images, has been obtained from all the participants and the parents\/legal guardians of minors.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"152"}}