{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:40:37Z","timestamp":1780465237482,"version":"3.54.1"},"reference-count":64,"publisher":"Walter de Gruyter GmbH","issue":"0","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"j_jpem-2018-0038_s_999\"><jats:title id=\"d852670e220\">Background<\/jats:title><jats:p>The short stature homeobox-containing (<jats:italic>SHOX<\/jats:italic>) gene strongly affects height. Therefore, a better understanding of<jats:italic>SHOX<\/jats:italic>haploinsufficiency could be advantageous to early diagnosis and treatment. We investigated the rate of<jats:italic>SHOX<\/jats:italic>haploinsufficiency in patients of short stature and documented their anthropometric measurements.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2018-0038_s_998\"><jats:title id=\"d852670e237\">Methods<\/jats:title><jats:p>Between 2010 and 2017, we evaluated 86 patients (70 females, 16 males; age 4.3\u201318 years) with clinical diagnoses of short stature and Madelung deformity (MD). Clinical abnormalities are presented for patients with MD with and without<jats:italic>SHOX<\/jats:italic>haploinsufficiency as determined by fluorescence<jats:italic>in situ<\/jats:italic>hybridisation (FISH).<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2018-0038_s_997\"><jats:title id=\"d852670e251\">Results<\/jats:title><jats:p>According to our inclusion criteria, 78 of 86 patients (70 females, 16 males) had short stature (height &lt;\u22122.5 standard deviation [SD]) and a family history suggestive of short stature. Eight patients had short stature, a family history suggestive of short stature and MD. MD was obvious in eight children in radiographic examinations. Although five of these had no deletion of<jats:italic>SHOX<\/jats:italic>, three had deletion of this gene. The deletion detection rate was 37.5% in the individuals with short stature and MD, i.e. Leri-Weill dyschondrosteosis syndrome (LWS), whilst no deletions were detected in the individuals with only short stature. One individual responded well to growth hormone (GH) treatment for the first 2 years but then developed an intolerance with persistently elevated insulin-like growth factor-1 (IGF-1) levels.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2018-0038_s_996\"><jats:title id=\"d852670e262\">Conclusions<\/jats:title><jats:p>As we likely missed cases due to our methodology, the routine analysis for<jats:italic>SHOX<\/jats:italic>screening should be firstly multiplex ligation-dependent probe amplification (MLPA). The incidence of MD may have been higher in the cohort if X-rays were performed in all individuals. GH treatment was not well tolerated in one case due to persistently elevated IGF-1 levels, and long-term evaluations of patients with<jats:italic>SHOX<\/jats:italic>deficiency are required.<\/jats:p><\/jats:sec>","DOI":"10.1515\/jpem-2018-0038","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T09:03:28Z","timestamp":1539767008000},"source":"Crossref","is-referenced-by-count":1,"title":["SHOX gene deletion screening by FISH in children with short stature and Madelung deformity and their characteristics"],"prefix":"10.1515","volume":"0","author":[{"given":"Erdal","family":"Kurnaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eenay","family":"Sava\u015f-Erdeve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semra","family":"\u00c7etinkaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehra","family":"Aycan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/ng0597-54","article-title":"Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome","volume":"16","year":"1997","journal-title":"Nat 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Genet"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.1210\/jc.2004-0591","article-title":"SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity","volume":"89","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"E11","DOI":"10.1136\/jmg.40.2.e11","article-title":"SHOX mutations detected by FISH and direct sequencing in patients with short stature","volume":"40","year":"2003","journal-title":"J Med Genet"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"E1257","DOI":"10.1210\/jc.2011-3460","article-title":"Genotypes and phenotypes of children with SHOX deficiency in France","volume":"97","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/ng0597-54","article-title":"Pseudoautosomal deletions encompassing a novel 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High incidence of SHOX anomalies in individuals with short stature","volume":"43","year":"2006","journal-title":"J Med Genet"},{"key":"ref581","first-page":"654","article-title":"Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)","volume":"42","year":"2004","journal-title":"Clin Chem Lab Med"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"E11","DOI":"10.1136\/jmg.40.2.e11","article-title":"SHOX mutations detected by FISH and direct sequencing in patients with short stature","volume":"40","year":"2003","journal-title":"J Med Genet"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"E1257","DOI":"10.1210\/jc.2011-3460","article-title":"Genotypes and phenotypes of children with SHOX deficiency in France","volume":"97","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref281","first-page":"987","article-title":"Familial growth and skeletal features associated with SHOX haploinsufficiency","volume":"16","year":"2003","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000197874","article-title":"Height gains in response to growth hormone treatment to final height are similar in patients with SHOX deficiency and Turner syndrome","volume":"71","year":"2009","journal-title":"Horm Res"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/pr.2016.233","article-title":"Prevalence of SHOX haploinsufficiency among short statured children","volume":"81","year":"2017","journal-title":"Pediatr Res"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1210\/jcem.86.12.8125","article-title":"Phenotypes associated with SHOX deficiency","volume":"86","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/ajmg.10422","article-title":"Complete SHOX 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height","volume":"467","year":"2010","journal-title":"Nature"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/sj.ejhg.5200402","article-title":"Phenotypic variation and genetic heterogeneity in L\u00e9ri-Weill syndrome","volume":"8","year":"2000","journal-title":"Eur J Hum Genet"},{"key":"ref521","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng0198-70","article-title":"Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis","volume":"19","year":"1998","journal-title":"Nat Genet"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/sj.ejhg.5200402","article-title":"Phenotypic variation and genetic heterogeneity in L\u00e9ri-Weill syndrome","volume":"8","year":"2000","journal-title":"Eur J Hum Genet"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/ajmg.10422","article-title":"Complete SHOX deficiency causes Langer mesomelic dysplasia","volume":"110","year":"2002","journal-title":"Am J Med Genet"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10038-006-0074-5","article-title":"Identification and characterization of different SHOX gene deletions in patients with Leri-Weill dyschondrosteosys by MLPA assay","volume":"52","year":"2007","journal-title":"J Hum Genet"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000329359","article-title":"Clinical and radiological characteristics of 22 children with SHOX anomalies and familial short stature suggestive of L\u00e9ri-Weill dyschondrosteosis","volume":"76","year":"2011","journal-title":"Horm Res Paediatr"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4274\/jcrpe.2307","article-title":"Investigation of SHOX gene mutations in Turkish patients with \u0131diopathic short stature","volume":"8","year":"2016","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1210\/jcem.87.3.8328","article-title":"Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature","volume":"87","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00431-013-2212-3","article-title":"Sitting height and sitting height\/height ratio references for Turkish children","volume":"173","year":"2014","journal-title":"Eur J Pediatr"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4274\/jcrpe.2307","article-title":"Investigation of SHOX gene mutations in Turkish patients with \u0131diopathic short stature","volume":"8","year":"2016","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1136\/jmg.2006.040998","article-title":"French SHOX 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High incidence of SHOX anomalies in individuals with short stature","volume":"43","year":"2006","journal-title":"J Med Genet"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1365-2265.2006.02698.x","article-title":"SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: frequency and phenotypic variability","volume":"66","year":"2007","journal-title":"Clin Endocrinol"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1210\/jcem.86.12.8125","article-title":"Phenotypes associated with SHOX deficiency","volume":"86","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref571","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00431-013-2212-3","article-title":"Sitting height and sitting height\/height ratio references for Turkish children","volume":"173","year":"2014","journal-title":"Eur J 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haploinsufficiency","volume":"16","year":"2003","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref311","first-page":"997","article-title":"Effect of 24 months of recombinant growth hormone on height and body proportions in SHOX haploinsufficiency","volume":"16","year":"2003","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref621","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000197874","article-title":"Height gains in response to growth hormone treatment to final height are similar in patients with SHOX deficiency and Turner syndrome","volume":"71","year":"2009","journal-title":"Horm Res"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00439-001-0609-y","article-title":"Analysis of short stature homeobox-containing gene (SHOX) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity","volume":"109","year":"2001","journal-title":"Hum Genet"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.gene.2011.10.011","article-title":"SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and L\u00e9ri-Weill dyschondrosteosis","volume":"491","year":"2012","journal-title":"Gene"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.gene.2011.10.011","article-title":"SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and L\u00e9ri-Weill dyschondrosteosis","volume":"491","year":"2012","journal-title":"Gene"},{"key":"ref591","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10038-006-0074-5","article-title":"Identification and characterization of different SHOX gene deletions in patients with Leri-Weill dyschondrosteosys by MLPA assay","volume":"52","year":"2007","journal-title":"J Hum Genet"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/ajmg.a.20198","article-title":"Deletion of the SHOX gene in patients with short stature of unknown cause","volume":"119A","year":"2003","journal-title":"Am J Med Genet A"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"280","DOI":"10.4274\/jcrpe.2183","article-title":"Reference values for weight, height, head circumference, and body mass index in Turkish children","volume":"7","year":"2015","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"ref651","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/B978-1-4557-4858-7.00025-1","volume-title":"Pediatric endocrinology.","year":"2014"}],"container-title":["Journal of Pediatric Endocrinology and 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