{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:22:52Z","timestamp":1787692972309,"version":"build-2784847793"},"reference-count":27,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873633"],"award-info":[{"award-number":["81873633"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National key research and development","award":["2018YFC1002501"],"award-info":[{"award-number":["2018YFC1002501"]}]},{"name":"Provincial Science and Technology Foundation of Guangxi","award":["AB16380214"],"award-info":[{"award-number":["AB16380214"]}]},{"name":"Health Department of Guangxi Province","award":["Z20190692"],"award-info":[{"award-number":["Z20190692"]}]},{"name":"Health Department of Guangxi Province","award":["SQ2018YFC100101"],"award-info":[{"award-number":["SQ2018YFC100101"]}]},{"name":"Medical and Health Appropriate Technology Development and Application","award":["S2020060"],"award-info":[{"award-number":["S2020060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Aggrecan, encoded by the ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Over 1000 unrelated short stature patients ascertained across China were genetically evaluated by next-generation sequencing\u2013based test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>We identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort; it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, 5 of 11 ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SD score improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data suggest that ACAN mutation is 1 of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab088","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T20:16:14Z","timestamp":1613852174000},"page":"e2711-e2719","source":"Crossref","is-referenced-by-count":41,"title":["A High Proportion of Novel\n                    <i>ACAN<\/i>\n                    Mutations and Their Prevalence in a Large Cohort of Chinese Short Stature Children"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7925-3937","authenticated-orcid":false,"given":"Li","family":"Lin","sequence":"first","affiliation":[{"name":"Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children\u2019s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[{"name":"Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children\u2019s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsi","family":"Luo","sequence":"additional","affiliation":[{"name":"Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children\u2019s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Affiliation Children\u2019s Hospital of Nanchang University, Jiangxi Provincial Children\u2019s Hospital, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliation Children\u2019s Hospital of Nanchang University, Jiangxi Provincial Children\u2019s Hospital, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Ge","sequence":"additional","affiliation":[{"name":"Linyi Maternal and Child Health Care Hospital, Linyi, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maimaiti","family":"Mireguli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wei","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Affiliated to Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihua","family":"Yang","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Affiliated to Zhengzhou University, Zhengzhou, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Child Health, Women and Children\u2019s Hospital, School of Medicine, Xiamen University, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Child Health, Women and Children\u2019s Hospital, School of Medicine, Xiamen University, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Child Health, Women and Children\u2019s Hospital, School of Medicine, Xiamen University, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical School, Huazhong University of Science 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