{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:43:41Z","timestamp":1791035021009,"version":"4.1.0"},"reference-count":31,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, as well as early-onset joint disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to evaluate the efficacy and safety of recombinant human GH (rhGH) on linear growth in ACAN-deficient children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Open-label, single-arm, prospective study over 3 years recruiting 10 treatment-na\u00efve patients with heterozygous mutations in ACAN, age \u22652 years, prepubertal, and normal IGF-I concentration. Patients were treated with rhGH (initially, 50\u2005mcg\/kg\/day). Main outcomes were change in (\u0394) height SD score (HtSDS) and height velocity (HV).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten patients (6 females) enrolled with median chronological age (CA) of 5.6 years (range, 2.4-9.7). Baseline median HtSDS, HV, and bone age\/CA were \u22122.5 (range, \u22124.3 to \u22121.1), 5.2\u2005cm\/year (range, 3.8 to 7.1), and 1.2 (range, 0.9 to 1.5), respectively. The cumulative median \u0394HtSDS over 3 years was +1.21 (range, +0.82 to +1.94). Median HV increased to 8.3\u2005cm\/year (range, 7.3-11.2), 7.7\u2005cm\/year (range, 5.9-8.8), and 6.8\u2005cm\/year (range, 4.9-8.6) during years 1, 2, and 3, respectively. The median \u0394 predicated adult height was +6.8\u2005cm over 3 years. Four female subjects entered puberty; nevertheless, median \u0394bone age\/CA was \u22120.1. No adverse events related to rhGH were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Linear growth improved in a cohort of ACAN-deficient patients treated with rhGH, albeit somewhat attenuated in older participants who entered puberty. Longitudinal follow-up is needed to assess the long-term efficacy of rhGH and adult height outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvae177","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T15:24:45Z","timestamp":1728487485000},"source":"Crossref","is-referenced-by-count":9,"title":["Treatment of Short Stature in Aggrecan-deficient Patients With Recombinant Human GH: 3-year Response"],"prefix":"10.1210","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-2357","authenticated-orcid":false,"given":"Gajanthan","family":"Muthuvel","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"Department of Pediatrics, University of Cincinnati , Cincinnati, OH 45267 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-0262","authenticated-orcid":false,"given":"Andrew","family":"Dauber","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Children's National Hospital , Washington, DC 20010 ,","place":["USA"]},{"name":"Department of Pediatrics, George Washington University School of Medicine and Health Sciences , Washington, DC 20052 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirene","family":"Alexandrou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, The University of Iowa Stead Family Children's Hospital , Iowa City, IA 52242 ,","place":["USA"]},{"name":"Department of Pediatrics, University of Iowa , Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Tyzinski","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Hwa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"Department of Pediatrics, University of Cincinnati , Cincinnati, OH 45267 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2398-9520","authenticated-orcid":false,"given":"Philippe","family":"Backeljauw","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"Department of Pediatrics, University of Cincinnati , Cincinnati, OH 45267 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"issue":"2","key":"2025021210524915800_bvae177-B1","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S0021-9258(17)35257-2","article-title":"Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms","volume":"266","author":"Doege","year":"1991","journal-title":"J Biol Chem"},{"issue":"2","key":"2025021210524915800_bvae177-B2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ydbio.2009.02.024","article-title":"Aggrecan modulation of growth plate morphogenesis","volume":"329","author":"Domowicz","year":"2009","journal-title":"Dev Biol"},{"issue":"1","key":"2025021210524915800_bvae177-B3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/sj.cr.7290106","article-title":"Structure and function of aggrecan","volume":"12","author":"Kiani","year":"2002","journal-title":"Cell Res"},{"issue":"4\/5","key":"2025021210524915800_bvae177-B4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1023\/A:1025344332099","article-title":"Chondrodysplasia of gene knockout mice for aggrecan and link protein","volume":"19","author":"Watanabe","year":"2002","journal-title":"Glycoconj J"},{"issue":"8","key":"2025021210524915800_bvae177-B5","doi-asserted-by":"crossref","first-page":"E1510","DOI":"10.1210\/jc.2014-1332","article-title":"Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations","volume":"99","author":"Nilsson","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2025021210524915800_bvae177-B6","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1210\/jc.2016-3313","article-title":"Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations","volume":"102","author":"Gkourogianni","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025021210524915800_bvae177-B7","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1210\/jc.2016-2941","article-title":"ACAN gene mutations in short children born SGA and response to growth hormone treatment","volume":"102","author":"van der Steen","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"7-8","key":"2025021210524915800_bvae177-B8","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1515\/jpem-2014-0450","article-title":"Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene","volume":"28","author":"Quintos","year":"2015","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"4","key":"2025021210524915800_bvae177-B9","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/ajmg.a.62639","article-title":"Clinical phenotype and musculoskeletal characteristics of patients with aggrecan deficiency","volume":"188","author":"Alexandrou","year":"2022","journal-title":"Am J Med Genet A"},{"key":"2025021210524915800_bvae177-B10","doi-asserted-by":"crossref","first-page":"1015954","DOI":"10.3389\/fendo.2022.1015954","article-title":"Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: novel ACAN heterozygous variants in eight Chinese children and a review of the literature","volume":"13","author":"Deng","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"8","key":"2025021210524915800_bvae177-B11","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1210\/js.2017-00229","article-title":"Aggrecan mutations in nonfamilial short stature and short stature without accelerated skeletal maturation","volume":"1","author":"Tatsi","year":"2017","journal-title":"J Endocr Soc"},{"issue":"5","key":"2025021210524915800_bvae177-B12","doi-asserted-by":"crossref","first-page":"e2103","DOI":"10.1210\/clinem\/dgab904","article-title":"Treatment of short stature in aggrecan-deficient patients with recombinant human growth hormone: 1-year response","volume":"107","author":"Muthuvel","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2025021210524915800_bvae177-B13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000455850","article-title":"New genetic diagnoses of short stature provide insights into local regulation of childhood growth","volume":"88","author":"Andrade","year":"2017","journal-title":"Horm Res Paediatr"},{"issue":"9","key":"2025021210524915800_bvae177-B14","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1210\/jc.2014-1506","article-title":"Genetic evaluation of short stature","volume":"99","author":"Dauber","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2025021210524915800_bvae177-B15","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jpeds.2012.07.055","article-title":"Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorder","volume":"162","author":"Dauber","year":"2013","journal-title":"J Pediatr"},{"issue":"11","key":"2025021210524915800_bvae177-B16","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.4158\/EP-2019-0518","article-title":"Growth-promoting therapies may be useful in short stature patients with nonspecific skeletal abnormalities caused by acan heterozygous mutations. Six Chinese cases and literature review","volume":"26","author":"Liang","year":"2020","journal-title":"Endocr Pract"},{"issue":"7","key":"2025021210524915800_bvae177-B17","doi-asserted-by":"crossref","first-page":"e2711","DOI":"10.1210\/clinem\/dgab088","article-title":"A high proportion of novel ACAN mutations and their prevalence in a large cohort of Chinese short stature children","volume":"106","author":"Lin","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2025021210524915800_bvae177-B18","doi-asserted-by":"crossref","first-page":"891040","DOI":"10.3389\/fgene.2022.891040","article-title":"The spectrum of ACAN gene mutations in a selected Chinese cohort of short stature: genotype-phenotype correlation","volume":"13","author":"Wu","year":"2022","journal-title":"Front Genet"},{"issue":"1","key":"2025021210524915800_bvae177-B19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12881-018-0591-z","article-title":"Novel aggrecan variant, p. Gln2364Pro, causes severe familial nonsyndromic adult short stature and poor growth hormone response in Chinese children","volume":"19","author":"Xu","year":"2018","journal-title":"BMC Med Genet"},{"key":"2025021210524915800_bvae177-B20","doi-asserted-by":"crossref","first-page":"819074","DOI":"10.3389\/fped.2022.819074","article-title":"Evaluation of growth hormone therapy in seven Chinese children with familial short stature caused by Novel ACAN variants","volume":"10","author":"Sun","year":"2022","journal-title":"Front Pediatr"},{"key":"2025021210524915800_bvae177-B21","doi-asserted-by":"crossref","first-page":"708864","DOI":"10.3389\/fgene.2021.708864","article-title":"Retrospective diagnosis of a novel ACAN pathogenic variant in a family with short stature: a case report and review of the literature","volume":"12","author":"Mancioppi","year":"2021","journal-title":"Front Genet"},{"key":"2025021210524915800_bvae177-B22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpeds.2020.06.051","article-title":"Sitting height to standing height ratio reference charts for children in the United States","volume":"226","author":"Hawkes","year":"2020","journal-title":"J Pediatr"},{"issue":"6","key":"2025021210524915800_bvae177-B23","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1210\/jc.2013-4455","article-title":"Age-based reference ranges for annual height velocity in US children","volume":"99","author":"Kelly","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2025021210524915800_bvae177-B24","first-page":"1","article-title":"Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development","volume":"52","author":"Prader","year":"1989","journal-title":"Helv Paediatr Acta Suppl"},{"issue":"5","key":"2025021210524915800_bvae177-B25","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1210\/jc.2013-3059","article-title":"Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations","volume":"99","author":"Bidlingmaier","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025021210524915800_bvae177-B26","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1210\/jc.2013-3060","article-title":"Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays","volume":"99","author":"Friedrich","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2025021210524915800_bvae177-B27","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/jc.2006-1409","article-title":"Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: two-year results of a randomized, controlled, multicenter trial","volume":"92","author":"Blum","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2025021210524915800_bvae177-B28","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.joca.2007.11.009","article-title":"Familial osteochondritis dissecans associated with early osteoarthritis and disproportionate short stature","volume":"16","author":"Stattin","year":"2008","journal-title":"Osteoarthr Cartil"},{"issue":"7","key":"2025021210524915800_bvae177-B29","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1210\/jc.2003-031457","article-title":"Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial","volume":"89","author":"Leschek","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2025021210524915800_bvae177-B30","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1210\/jcem.87.2.8225","article-title":"Final height gain by GH therapy in children with idiopathic short stature is dose dependent","volume":"87","author":"Wit","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025021210524915800_bvae177-B31","doi-asserted-by":"crossref","first-page":"456\u2013","DOI":"10.1159\/000535651","article-title":"Clinical characteristics of pathogenic ACAN variants and 3-year response to growth hormone treatment: real-world data","volume":"97","author":"Renes","year":"2024","journal-title":"Horm Res Paediatr"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvae177\/59714721\/bvae177.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/8\/12\/bvae177\/60776353\/bvae177.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/8\/12\/bvae177\/60776353\/bvae177.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T05:53:10Z","timestamp":1739339590000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvae177\/7817879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,10]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,10,29]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvae177","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,10,10]]},"article-number":"bvae177"}}