{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:47:27Z","timestamp":1780663647209,"version":"3.54.1"},"reference-count":39,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Short stature affects approximately 2% of children, representing one of the more frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions of the short stature homeobox-containing gene (<jats:italic>SHOX<\/jats:italic>) are found quite frequently in subjects with short stature. Haploinsufficiency of the <jats:italic>SHOX<\/jats:italic> gene causes short stature with highly variable clinical severity, ranging from isolated short stature without dysmorphic features to L\u00e9ri-Weill syndrome, and with no functional copy of the <jats:italic>SHOX<\/jats:italic> gene, Langer syndrome.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> To characterise the clinical and molecular spectrum of <jats:italic>SHOX<\/jats:italic> deficiency in childhood we assessed the association between genotype and phenotype in a large cohort of children of short stature from 14 countries.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> Screening of 1608 unrelated individuals with sporadic or familial short stature revealed <jats:italic>SHOX<\/jats:italic> mutations or deletions in 68 individuals (4.2%): complete deletions in 48 (70.6%), partial deletions in 4 (5.9%) and point mutations in 16 individuals (23.5%). Although mean height standard deviation score (SDS) was not different between participants of short stature with or without identified <jats:italic>SHOX<\/jats:italic> gene defects (\u20132.6 vs \u20132.6), detailed examination revealed that certain bone deformities and dysmorphic signs, such as short forearm and lower leg, cubitus valgus, Madelung deformity, high-arched palate and muscular hypertrophy, differed markedly between participants with or without <jats:italic>SHOX<\/jats:italic> gene defects (p&lt;0.001). Phenotypic data were also compared for 33 children with Turner syndrome in whom haploinsufficiency of <jats:italic>SHOX<\/jats:italic> is thought to be responsible for the height deficit.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion:<\/jats:bold> A phenotype scoring system was developed that could assist in identifying the most appropriate subjects for <jats:italic>SHOX<\/jats:italic> testing. This study offers a detailed genotype-phenotype analysis in a large cohort of children of short stature, and provides quantitative clinical guidelines for testing of the <jats:italic>SHOX<\/jats:italic> gene.<\/jats:p>","DOI":"10.1136\/jmg.2006.046581","type":"journal-article","created":{"date-parts":[[2006,12,20]],"date-time":"2006-12-20T20:24:23Z","timestamp":1166646263000},"page":"306-313","source":"Crossref","is-referenced-by-count":185,"title":["Genotypes and phenotypes in children with short stature: clinical indicators of <i>SHOX<\/i> haploinsufficiency"],"prefix":"10.1136","volume":"44","author":[{"given":"Gudrun","family":"Rappold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner F","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena P","family":"Shavrikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda J","family":"Crowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Roeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmian A","family":"Quigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith L","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Niesler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2006,12,20]]},"reference":[{"key":"2025100511385890000_44.5.306.1","doi-asserted-by":"publisher","DOI":"10.1159\/000073226"},{"key":"2025100511385890000_44.5.306.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0092"},{"key":"2025100511385890000_44.5.306.3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.26.3083"},{"key":"2025100511385890000_44.5.306.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1341"},{"key":"2025100511385890000_44.5.306.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-54"},{"key":"2025100511385890000_44.5.306.6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.5.695"},{"key":"2025100511385890000_44.5.306.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.3.1402"},{"key":"2025100511385890000_44.5.306.8","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.6.e33"},{"key":"2025100511385890000_44.5.306.9","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.10.758"},{"key":"2025100511385890000_44.5.306.10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030136"},{"key":"2025100511385890000_44.5.306.11","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.040998"},{"key":"2025100511385890000_44.5.306.12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307006200"},{"key":"2025100511385890000_44.5.306.13","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032230"},{"key":"2025100511385890000_44.5.306.14","doi-asserted-by":"publisher","DOI":"10.1142\/S0218810401000424"},{"key":"2025100511385890000_44.5.306.15","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.1.1"},{"key":"2025100511385890000_44.5.306.16","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10125"},{"key":"2025100511385890000_44.5.306.17","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-67"},{"key":"2025100511385890000_44.5.306.18","doi-asserted-by":"publisher","DOI":"10.1038\/1734"},{"key":"2025100511385890000_44.5.306.19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.12.4613"},{"key":"2025100511385890000_44.5.306.20","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.51.197"},{"key":"2025100511385890000_44.5.306.21","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200402"},{"key":"2025100511385890000_44.5.306.22","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1501"},{"key":"2025100511385890000_44.5.306.23","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1409"},{"key":"2025100511385890000_44.5.306.24","unstructured":"Fl\u00fcgel B, Greil H, Sommer K. 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