{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:40:27Z","timestamp":1787244027627,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Heterozygous variants in the\n                    <jats:italic>ACAN<\/jats:italic>\n                    gene are a recognized cause of short stature. We aimed to evaluate the response to growth hormone (GH) treatment in members of an extended family carrying an\n                    <jats:italic>ACAN<\/jats:italic>\n                    variant. Clinical and laboratory data of five related children were retrospectively collected. GH therapy was initiated at a mean age of 3.2\u2009\u00b1\u20092.1\u2009years and treated for 6.4\u2009\u00b1\u20095.0\u2009years. The height standard deviation scores (SDS) increased from \u22123.3\u2009\u00b1\u20091.0 to \u22122.0\u2009\u00b1\u20091.1 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001), with a mean gain of 1.3\u2009\u00b1\u20090.3 SDS. The most notable increase in growth velocity SDS occurred during the first year of treatment (\u22120.5\u2009\u00b1\u20090.6 to 2.1\u2009\u00b1\u20091.2;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). No adverse effects were observed, and bone age did not advance significantly. Three children entered puberty between the ages of 10 and 11.6\u2009years and received adjunctive gonadotropin releasing hormone analog therapy. Genetic testing identified a heterozygous nonsense variant in the\n                    <jats:italic>ACAN<\/jats:italic>\n                    (c.2023C&gt;T; p.Arg675*). Our findings suggest that GH therapy can improve growth velocity in children with\n                    <jats:italic>ACAN<\/jats:italic>\n                    \u2010related short stature, though the degree of response varies even within the same family. The long\u2010term impact on final adult height remains to be elucidated.\n                  <\/jats:p>","DOI":"10.1111\/cge.70050","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T07:01:02Z","timestamp":1756105262000},"page":"374-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of Growth Hormone Treatment in Children From an Extended Family With\n                    <scp>\n                      <i>ACAN<\/i>\n                    <\/scp>\n                    \u2010Related Short Stature"],"prefix":"10.1111","volume":"109","author":[{"given":"Einat","family":"Shalev\u2010Goldman","sequence":"first","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Pediatric Endocrinology and Diabetes Unit, the Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Asaly","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Pediatric Endocrinology and Diabetes Unit, the Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Ityel","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"The Institute for Rare Diseases, the Danek Gertner Institute of Human Genetics Sheba Medical Center  Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Pode\u2010Shakked","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"The Institute for Rare Diseases, the Danek Gertner Institute of Human Genetics Sheba Medical Center  Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalit","family":"Modan\u2010Moses","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Pediatric Endocrinology and Diabetes Unit, the Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-4230","authenticated-orcid":false,"given":"Yael","family":"Levy\u2010Shraga","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Pediatric Endocrinology and Diabetes Unit, the Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel\u2010Hashomer 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