{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:56:58Z","timestamp":1792655818393,"version":"4.5.0"},"reference-count":23,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>SHOX (short stature homeobox-containing gene) mutations causing haploinsufficiency have been reported in some individuals with idiopathic short stature and in many patients with Leri-Weill-dyschondrosteosis. Around 80% of SHOX mutations are complete gene deletions, whereas diverse point mutations account for the rest. The aim of this study was to estimate the prevalence of SHOX mutations in children with idiopathic short stature and to give an unbiased characterization of the haploinsufficiency phenotype of such children. We recruited 140 children (61 girls), in our clinic, with idiopathic short stature, which was defined by the presence of normal IGF-I and free T4; a normal karyotype in females; the absence of endomysium antibodies, of chronic organic, psychological, or syndromatic disease; and by the lack of clear signs of any osteodysplasia. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Two highly polymorphic microsatellite markers located around the SHOX coding region (CA-SHOX repeat and DXYS233) were PCR-amplified with fluorescent primers and separated in an automatic sequencing machine. Analysis of parental DNA was performed in the probands who had only one fragment size of each of both markers. SHOX haploinsufficiency caused by a SHOX deletion was confirmed in three probands (2%), all females, who carried a de novo deletion through loss of the paternal allele. Their auxological data revealed a significant shortening of arms and legs in the presence of a low-normal sitting height, when compared with the other 137 children tested. Therefore, the extremities-trunk ratio (sum of leg length and arm span, divided by sitting height) for total height was significantly lower in the three SHOX haploinsufficient probands, in comparison with the whole group. This observation was confirmed with the auxological data of five additional patients (four females) previously diagnosed with SHOX haploinsufficiency; all but the youngest girl had height-adjusted extremities-trunk ratios more than 1 sd below the mean. All children with SHOX haploinsufficiency exhibited at least one characteristic radiological sign of Leri-Weill-dyschondrosteosis in their left-hand radiography, namely triangularization of the distal radial epiphysis, pyramidalization of the distal carpal row, or lucency of the distal ulnar border of the radius. Our observations suggest that it is rational to limit SHOX mutation screening to children with an extremities-trunk ratio less than 1.95 + 1\/2 height (m) and to add a critical judgment of the hand radiography.<\/jats:p>","DOI":"10.1210\/jc.2003-030136","type":"journal-article","created":{"date-parts":[[2003,10,13]],"date-time":"2003-10-13T17:42:51Z","timestamp":1066066971000},"page":"4891-4896","source":"Crossref","is-referenced-by-count":86,"title":["Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature"],"prefix":"10.1210","volume":"88","author":[{"given":"Gerhard","family":"Binder","sequence":"first","affiliation":[{"name":"University Children\u2019s Hospital, 72076 Tu\u0308bingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Ranke","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, 72076 Tu\u0308bingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Martin","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, 72076 Tu\u0308bingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071617261090000_R1","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","author":"Rao","year":"1997","journal-title":"Nat Genet"},{"key":"2020071617261090000_R2","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","author":"Rappold","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071617261090000_R3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/ng0198-67","article-title":"SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).","volume":"19","author":"Belin","year":"1998","journal-title":"Nat Genet"},{"key":"2020071617261090000_R4","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","author":"Shears","year":"1999","journal-title":"Nat Genet"},{"key":"2020071617261090000_R5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/sj.ejhg.5200402","article-title":"Phenotypic variation and genetic heterogeneity in Leri-Weill syndrome.","volume":"8","author":"Schiller","year":"2000","journal-title":"Eur J Hum Genet"},{"key":"2020071617261090000_R6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/ajmg.10228","article-title":"Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome).","volume":"106","author":"Cormier-Daire","year":"2001","journal-title":"Am J Med Genet"},{"key":"2020071617261090000_R7","first-page":"1491","article-title":"Une affection conge\u0301nitale et syme\u0301trique du de\u0301veloppement osseux: la dyschondroste\u0301ose.","volume":"35","author":"Leri","year":"1929","journal-title":"Bull Me\u0301m Soc Med Hosp"},{"key":"2020071617261090000_R8","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/hmg\/9.5.695","article-title":"The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome.","volume":"9","author":"Clement-Jones","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2020071617261090000_R9","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1093\/hmg\/10.26.3083","article-title":"The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator.","volume":"10","author":"Rao","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2020071617261090000_R10","doi-asserted-by":"crossref","first-page":"5672","DOI":"10.1210\/jcem.86.12.eg1201.8186","article-title":"A SHOX to the system.","volume":"86","author":"Rosenfeld","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071617261090000_R11","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1210\/jcem.86.12.8125","article-title":"Phenotypes associated with SHOX deficiency.","volume":"86","author":"Ross","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071617261090000_R12","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1210\/jcem.84.12.6289","article-title":"Skeletal features and growth pattern in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome.","volume":"84","author":"Kosho","year":"1999","journal-title":"J Clin Endocrinol 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