{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:22:46Z","timestamp":1787692966300,"version":"build-2784847793"},"reference-count":33,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context:<\/jats:title>\n                    <jats:p>Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We sought to characterize the phenotypic spectrum and response to growth-promoting therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods:<\/jats:title>\n                    <jats:p>One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and\/or Sanger sequencing. Clinical information was collected from the medical records.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Identified ACAN variants showed perfect cosegregation with phenotype. Adult individuals had mildly disproportionate short stature [median height, \u22122.8 standard deviation score (SDS); range, \u22125.9 to \u22120.9] and a history of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). No apparent genotype\u2013phenotype correlation was found between the type of ACAN mutation and the presence of joint complaints. Childhood height was less affected (median height, \u22122.0 SDS; range, \u22124.2 to \u22120.6). Most children with ACAN mutations had advanced bone age (bone age \u2212 chronologic age; median, +1.3 years; range, +0.0 to +3.7 years). Nineteen individuals had received growth hormone therapy with some evidence of increased growth velocity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. Many affected individuals developed early-onset osteoarthritis and degenerative disc disease, suggesting dysfunction of the articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2016-3313","type":"journal-article","created":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T14:07:00Z","timestamp":1479737220000},"page":"460-469","source":"Crossref","is-referenced-by-count":119,"title":["Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations"],"prefix":"10.1210","volume":"102","author":[{"given":"Alexandra","family":"Gkourogianni","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet and Karolinska University Hospital, Stockholm SE-171 76, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Andrew","sequence":"additional","affiliation":[{"name":"Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio 70941;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Tyzinski","sequence":"additional","affiliation":[{"name":"Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio 70941;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Crocker","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Douglas","sequence":"additional","affiliation":[{"name":"Genetics, Boston Children\u2019s Hospital, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Connecticut Children\u2019s Medical Center, Hartford, Connecticut 06106;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Women\u2019s and Children\u2019s Hospital, North Adelaide, South Australia 5006, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana F. A.","family":"Funari","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento (LIM\/42), Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-020, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Heath","sequence":"additional","affiliation":[{"name":"Institute of Medical and Molecular Genetics (INGEMM) and Skeletal Dysplasia Multidisciplinary Unit, Hospital Universitario La Paz, Universidad Aut\u00f3noma de Madrid, IdiPAZ, and CIBERER, ISCIII, Madrid 20849, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A. L.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento (LIM\/42), Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-020, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Kurtzman","sequence":"additional","affiliation":[{"name":"El Rio Community Health Center, Tucson, Arizona 85745;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"LaFranchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Lalani","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Human Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lebl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University in Prague and University Hospital in Motol, Prague 11636, Czech Republic;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuezhen","family":"Lin","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology and Metabolism, Baylor College of Medicine, Houston, Texas 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Los","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Newbern","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Phoenix Children\u2019s Hospital, Phoenix, Arizona 85016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Nowak","sequence":"additional","affiliation":[{"name":"Genetics, Boston Children\u2019s Hospital, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Phoenix Children\u2019s Hospital, Phoenix, Arizona 85016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadranka","family":"Popovic","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15237;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0160t\u011bp\u00e1nka","family":"Pr\u016fhov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University in Prague and University Hospital in Motol, Prague 11636, Czech 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