{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:48:58Z","timestamp":1787237338058,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To characterize the phenotype spectrum, diagnosis, and response to growth\u2010promoting therapy in patients with\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants causing familial short stature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three families with\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants causing short stature were reported. Similar cases in the literature were summarized, and the genotype and phenotype were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three novel heterozygous variants, c.757+1G&gt;A, (splicing), c.6229delG, p.(Asp2078Tfs*1), and c.6679C&gt;T, p.(Gln2227*) in the\n                      <jats:italic>ACAN<\/jats:italic>\n                      gene were identified. A total of 314 individuals with heterozygous variants from 105 families and 8 individuals with homozygous variants from 4 families were confirmed to have\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants from literature and our 3 cases. Including our 3 cases, the variants reported comprised 33 frameshift, 39 missense, 23 nonsense, 5 splicing, 4 deletion, and 1 translocation variants. Variation points are scattered throughout the gene, while exons 12, 15, and 10 were most common (25\/105, 11\/105, and 10\/105, respectively). Some identical variants existing in different families could be hot variants, c.532A&gt;T, p.(Asn178Tyr), c.1411C&gt;T, p.(Gln471*), c.1608C&gt;A, p.(Tyr536*), c.2026+1G&gt;A, (splicing), and c.7276G&gt;T, p.(Glu2426*). Short stature, early\u2010onset osteoarthritis, brachydactyly, midfacial hypoplasia, and early growth cessation were the common phenotypic features. The 48 children who received rhGH (and GnRHa) treatment had a significant height improvement compared with before (\u22122.18\u2009\u00b1\u20091.06 SD vs. \u22122.69\u2009\u00b1\u20090.95 SD,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The heights of children who received rhGH (and GnRHa) treatment were significantly improved compared with those of untreated adults (\u22122.20\u2009\u00b1\u20091.10 SD vs. \u22123.24\u2009\u00b1\u20091.14 SD,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study achieves a new understanding of the phenotypic spectrum, diagnosis, and management of individuals with\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants. No clear genotype\u2013phenotype relationship of patients with\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants was found. Gene sequencing is necessary to diagnose\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants that cause short stature. In general, appropriate rhGH and\/or GnRHa therapy can improve the adult height of affected pediatric patients caused by\n                      <jats:italic>ACAN<\/jats:italic>\n                      variants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.2439","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T03:14:15Z","timestamp":1712978055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genotype and phenotype in patients with\n                    <scp>\n                      <i>ACAN<\/i>\n                    <\/scp>\n                    gene variants: Three cases and literature review"],"prefix":"10.1002","volume":"12","author":[{"given":"Wei","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pulmonary Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Mi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"},{"name":"Department of Pediatrics Hangzhou Children's Hospital  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Fei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"},{"name":"Department of Pediatrics Jiaxing Second people's Hospital  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Fen","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan\u2010Ping","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4667-3636","authenticated-orcid":false,"given":"Chao\u2010Chun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Children's Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013\u20103525"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370223"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519\u2010023\u201000758\u2010y"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.165"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030136"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618\u2010017\u20100819\u20103"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1297\/cpe.26.119"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2017.33"},{"key":"e_1_2_13_10_1","volume-title":"Detection of ACAN gene mutation in a patient with dwarfism and spondylometaphyseal dysplasia and analysis of clinical factors influencing dwarfism. 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