{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:46Z","timestamp":1791561046354,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Short stature is clinically and genetically heterogeneous, and defects in the extracellular matrix of growth plate cartilage represent a key disease mechanism.\n                    <jats:italic>ACAN<\/jats:italic>\n                    encodes aggrecan, the major proteoglycan of the growth plate cartilage extracellular matrix. Heterozygous\n                    <jats:italic>ACAN<\/jats:italic>\n                    variants are a recognized cause of familial short stature, often associated with advanced bone age and early growth cessation, yet they show a broad phenotypic spectrum. We aimed to delineate the clinical and molecular spectrum of\n                    <jats:italic>ACAN<\/jats:italic>\n                    \u2010related short stature in a Turkish cohort. We retrospectively reviewed 47 individuals from 20 unrelated families with short stature (height\u2009\u2264\u2009\u22122 SDS) or predicted adult height\u2009&lt;\u2009\u22122 SDS. Anthropometric data, dysmorphic and musculoskeletal findings, radiologic assessments, and molecular genetic results were analyzed. Among 47 individuals (20 females, 27 males), 59.6% were children. Common clinical features included a high forehead, upslanted palpebral fissures, a depressed nasal bridge, low\u2010set anteverted ears, mild pectus deformity, and brachydactyly. Osteochondritis dissecans, early\u2010onset osteoarthritis, and advanced bone age were identified in 6.5%, 8.7%, and 28.6% of individuals, respectively. Vertebral findings included scoliosis (19.6%), increased lumbar lordosis (13%), and vertebral endplate changes (10.9%). Genetic testing revealed 15 heterozygous\n                    <jats:italic>ACAN<\/jats:italic>\n                    variants (2 previously reported in ClinVar; 13 novel): 6 nonsense, 2 splice\u2010site, 5 frameshift, and 2 missense. Overall, 45 patients carried pathogenic\/likely pathogenic variants (14 variants), and 2 carried VUS (1 variant).\n                    <jats:italic>ACAN<\/jats:italic>\n                    \u2010related short stature represents an important subset of familial short stature. Skeletal and musculoskeletal findings may aid diagnosis, but advanced bone age is not consistent and bone age is often appropriate for chronological age.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70282","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T03:30:06Z","timestamp":1787110206000},"page":"2507-2518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>ACAN<\/i>\n                    <\/scp>\n                    \u2010Related Short Stature and Skeletal Dysplasia: Expanding the Phenotypic and Genotypic Spectrum in a 47 Patient Cohort From Turkey"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-9910","authenticated-orcid":false,"given":"Abdulkerim","family":"Kolkiran","sequence":"first","affiliation":[{"name":"Department of Pediatric Genetics Ankara Etlik City Hospital  Ankara 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Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2109-139X","authenticated-orcid":false,"given":"Berna","family":"U\u00e7an","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology University of Health Sciences, Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-2208","authenticated-orcid":false,"given":"Ahmet","family":"Kablan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-9792","authenticated-orcid":false,"given":"Elifcan","family":"Ta\u015fdelen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2187-1554","authenticated-orcid":false,"given":"Firdevs Din\u00e7soy","family":"Bir","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8755-7714","authenticated-orcid":false,"given":"Keziban Asl\u0131","family":"Bala","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara Etlik City Hospital  Ankara Turkey"},{"name":"Department of Pediatric Endocrinology University of Health Sciences, Ankara Etlik City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-4420","authenticated-orcid":false,"given":"Ay\u015fe Derya","family":"Bulu\u015f","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology University of Health Sciences, Ankara Atat\u00fcrk Sanatorium Training and Research Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9024-6283","authenticated-orcid":false,"given":"Hande Nur","family":"\u015eengil","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara Bilkent City Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7888-7295","authenticated-orcid":false,"given":"G\u00f6n\u00fcl","family":"B\u00fcy\u00fcky\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara Bilkent City Hospital  Ankara Turkey"},{"name":"Department of Pediatric Endocrinology Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University Faculty of Medicine  Ankara 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