{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T19:25:57Z","timestamp":1781205957601,"version":"3.54.1"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>ACAN<\/jats:italic> (OMIM 155760) is located on chromosome 15q26 and encodes the production of aggrecan. Aggrecan is a large chondroitin sulfate proteoglycan with a molecular weight of 254\u00a0kDa and contains 2530 amino acids. It is a critical structural component of the extracellular matrix of cartilage, including growth plate, articular, and intervertebral disk cartilage. It plays a key role in bone development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we describe two pedigrees with loss\u2010of\u2010function variants in <jats:italic>ACAN<\/jats:italic>. Whole exome sequencing was performed for the probands from each family. We illustrate the clinical variability associated with <jats:italic>ACAN<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proband of pedigree A manifested short stature, relative macrocephaly, mild flat nasal bridge, low\u2010set ears, short neck, and short thumbs. The proband of pedigree B had short height, abnormal vertebral development, and central precocious puberty. By trio\u2010based whole exome sequencing and in silico analyses, we identified two de novo heterozygous variants of <jats:italic>ACAN<\/jats:italic>: NM_013227.4: c.116dupT, p.Arg40Glufs*51 and NM_013227.4: c.2367delC, p.Ser790Glnfs*20 (accession number: AC103982.10).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The clinical manifestations of <jats:italic>ACAN<\/jats:italic> gene variants are diverse. <jats:italic>ACAN<\/jats:italic> gene variants are important genetic factors for short stature and should be considered as the differential diagnosis of children with idiopathic short stature (ISS).<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1823","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T07:47:21Z","timestamp":1633420041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of novel <i>ACAN<\/i> mutations in two Chinese families and genotype\u2013phenotype correlation in patients with 74 pathogenic <i>ACAN<\/i> variations"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5839-0190","authenticated-orcid":false,"given":"Ming","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-3896","authenticated-orcid":false,"given":"Ying","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-017-0819-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2017.33"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-019-0719-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000241"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3313"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/444401"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ17-0150"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12465-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.04.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP-2019-0518"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1332"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02288"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2014-0450"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13581"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.018"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0771"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00229"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.12.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2941"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000021635"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0591-z"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0730-6"},{"issue":"6","key":"e_1_2_9_24_1","first-page":"463","article-title":"Familial short stature caused by ACAN gene mutation: a familial case report","volume":"36","author":"Zeng T.","year":"2018","journal-title":"Journal of Clinical Pediatrics"}],"container-title":["Molecular Genetics &amp; 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