{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:36:33Z","timestamp":1768898193739,"version":"3.49.0"},"reference-count":32,"publisher":"BMJ","issue":"11","funder":[{"name":"Scientific Research Project of Hunan Provincial Health Commission","award":["B202306048930"],"award-info":[{"award-number":["B202306048930"]}]},{"name":"Project of Clinical Research Center for Hereditary Birth Defects and Rare Diseases of Hunan Province","award":["2023S-K4053"],"award-info":[{"award-number":["2023S-K4053"]}]},{"name":"Special fund of the Hunan provincial key laboratory of pediatric orthopedics","award":["2023TP1019"],"award-info":[{"award-number":["2023TP1019"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31501017"],"award-info":[{"award-number":["31501017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key R&D Program of China","award":["2022YFC2703700"],"award-info":[{"award-number":["2022YFC2703700"]}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["2023JJ40343"],"award-info":[{"award-number":["2023JJ40343"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["2024JJ5219"],"award-info":[{"award-number":["2024JJ5219"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,7,3]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      While\n                      <jats:italic>AUTS2<\/jats:italic>\n                      is recognised as a pivotal neurodevelopmental gene, its role in skeletal morphogenesis has remained unexplored. We investigated the contribution of\n                      <jats:italic>AUTS2<\/jats:italic>\n                      to radioulnar synostosis (RUS) and associated skeletal dysplasias through integrated molecular and phenotypic analyses of unrelated probands.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Comprehensive genetic profiling was performed on patients with RUS, including G-banding karyotyping, translocation breakpoint mapping via low-coverage whole-genome sequencing with PCR\/Sanger validation, CNV detection using SNP array (Infinium OmniZhongHua-8) and qPCR, and exome sequencing followed by orthogonal Sanger confirmation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four novel pathogenic\n                      <jats:italic>AUTS2<\/jats:italic>\n                      variants were identified from four unrelated patients: a balanced translocation [46,XY,t(7;21)(q11.22;q21.1)] disrupting intron 5 (hg19:chr7:71,845,797); a heterozygous 2.99\u2009Mb deletion (hg19:7q11.22[67,488,531\u201370,480,818]) spanning AUTS2 and flanking loci; and two de novo frameshift insertions (c.47_48insG; c.864_865insGGACTGTTGCAAAGAGCCA). All variants impaired the full-length\n                      <jats:italic>AUTS2<\/jats:italic>\n                      transcript. Affected individuals exhibited RUS accompanied by additional skeletal anomalies (micrognathia, short stature, dysplasia of hip joint, tight heel cords) and other AUTS2 syndrome features. Notably, phenotypic overlap with Tsukahara syndrome (OMIM 603438) was observed, suggesting potential diagnostic continuity between these entities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study establishes\n                      <jats:italic>AUTS2<\/jats:italic>\n                      as a critical regulator of skeletal development, with molecular disruptions directly linked to RUS pathogenesis and broader skeletal dysmorphogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2025-110886","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T21:40:24Z","timestamp":1752702024000},"page":"677-681","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["<i>AUTS2<\/i>\n                    disruption underlies radioulnar synostosis and skeletal dysmorphogenesis: evidence from four unrelated cases"],"prefix":"10.1136","volume":"62","author":[{"given":"Cheng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Hunan Children's Hospital, School of Pediatrics, University of South China, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Affiliated Children's Hospital of Xiangya School of Medicine (Hunan Children's Hospital), Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hunan Children's Hospital, School of Pediatrics, University of South China, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanchun","family":"Yang","sequence":"additional","affiliation":[{"name":"Salus Biomed, 1-2001, Hengtaiyu Research Park, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Salus Biomed, 1-2001, Hengtaiyu Research Park, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The Affiliated Children's Hospital of Xiangya School of Medicine (Hunan Children's Hospital), Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Affiliated Children's Hospital of Xiangya School of Medicine (Hunan Children's Hospital), Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-6139","authenticated-orcid":false,"given":"Zhuo","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, MOE Key Lab of Rare Pediatric Diseases, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8673-1589","authenticated-orcid":false,"given":"Yongjia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Affiliated Children's Hospital of Xiangya School of Medicine (Hunan Children's Hospital), Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"2025102806151061000_62.11.677.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2013.08.001"},{"key":"2025102806151061000_62.11.677.2","first-page":"549","article-title":"Twins with autism and mental retardation associated with balanced (7;20) chromosomal translocation","volume":"57","author":"de la Barra","year":"1986","journal-title":"Rev Chil Pediatr"},{"key":"2025102806151061000_62.11.677.3","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6810"},{"key":"2025102806151061000_62.11.677.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0409-1"},{"key":"2025102806151061000_62.11.677.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.12.011"},{"key":"2025102806151061000_62.11.677.6","doi-asserted-by":"crossref","first-page":"101820","DOI":"10.1016\/j.isci.2020.101820","article-title":"AUTS2 Governs Cerebellar 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Inhibition","volume":"19","author":"Geng","year":"2023","journal-title":"Stem Cell Rev Rep"},{"key":"2025102806151061000_62.11.677.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.09.020"},{"key":"2025102806151061000_62.11.677.30","doi-asserted-by":"crossref","unstructured":"Erdogan EN , Cheng CV , Caraffi SG , et al . Further Delineation of the AUTS2 HX Repeat Domain-Related Phenotype. Am J Med Genet A 2025.:e64093. doi:10.1002\/ajmg.a.64093","DOI":"10.1002\/ajmg.a.64093"},{"key":"2025102806151061000_62.11.677.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.11.004"},{"key":"2025102806151061000_62.11.677.32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature13921","article-title":"An AUTS2-Polycomb complex activates gene expression in the CNS","volume":"516","author":"Gao","year":"2014","journal-title":"Nature New Biol"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2025-110886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:06:12Z","timestamp":1761663972000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2025-110886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,10,20]]},"published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1136\/jmg-2025-110886"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2025-110886","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}