{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:47:37Z","timestamp":1761511657633},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":3010,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>OBJECTIVE To investigate the hypothesis that intracellular, dominant\u2010negative mutations of the growth hormone receptor (GHR) exist in children with idiopathic short stature (ISS) and partial growth hormone insensitivity (GHI).<\/jats:p><jats:p>SUBJECTS We studied 31 children aged 4.55\u201313.14 years with ISS (height \u2264\u20101.8 standard deviation scores, UK standards 1990). GH provocation tests (glucagon 15\u03bcg kg<jats:sup>\u22121<\/jats:sup> i.m.) excluded GH deficiency In all subjects. Serum IGF\u2010I levels were below the 50th centile for age in all subjects and below the 10th centile in 64.5% of cases. GH binding protein levels were normal in the 24 subjects in whom It was measured (mean 25.2%; range 10\u201342.6%).<\/jats:p><jats:p>METHODS Exons 9 and 10 of the GHR were amplified by PCR from leucocyte\u2010derived DNA. Samples were directly sequenced on the ABI 377 DNA analyser using the \u221221 M13 dye primer cycle sequencing protocol for optimum heterozygote detection.<\/jats:p><jats:p>RESULTS No abnormalities were detected in exon 9 which encodes the proline\u2010rich box 1 motif. In exon 10 two sequence variants were found; a heterozygous, single base alteration (TCT to TCC) in codon 325 which does not change the amino acid sequence in one patient, and the L5261 variant in 24 subjects. L5261 is a conservative amino acid change and had an allele frequency of 0.53 in our patients, which is similar to that reported in a control population.<\/jats:p><jats:p>CONCLUSIONS The apparent partial growth hormone insensitivity in this group of idiopathic short\u2010stature subjects is not related to heterozygous, dominant\u2010negative variants of the intracellular signalling domain of the GHR. Hence it is likely that other genetic and environmental factors may be involved.<\/jats:p>","DOI":"10.1046\/j.1365-2265.2000.00940.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:44:30Z","timestamp":1047379470000},"page":"463-469","source":"Crossref","is-referenced-by-count":14,"title":["Analysis of the intracellular signalling domain of the human growth hormone receptor in children with idiopathic short stature"],"prefix":"10.1111","volume":"52","author":[{"given":"Linda B.","family":"Johnston","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farzana","family":"Pashankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Camacho\u2010H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin 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