{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T02:19:48Z","timestamp":1786760388046,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T00:00:00Z","timestamp":1333584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objectives\u2002<\/jats:bold> Growth hormone insensitivity syndrome (GHIS) is characterized by extreme short stature and resistance to the actions of growth hormone (GH). The heterogeneity ranges from the most severe form, known as Laron syndrome, to less severe phenotypes like idiopathic short stature and partial GH insensitivity. Here, we aimed to identify and characterize the molecular cause of severe short stature in a patient with resistance to GH treatment.<\/jats:p><jats:p><jats:bold>Patient\u2002<\/jats:bold> We describe a male patient born small for gestational age [38\u2003weeks gestation, length 38\u00b75\u2003cm; \u22127\u00b78 standard deviation score (SDS), weight 1350\u2003g; \u22124\u00b784\u2003SDS]. At the age of 7\u2003years (109\u00b77\u2003cm; \u22122\u00b789\u2003SD), he received GH treatment (1\u2003mg\/m<jats:sup>2<\/jats:sup>\/day) for 1\u2003year without any increase in height SDS, IGF\u2010I or IGFBP\u20103 levels. Double\u2010GH\u2010dose treatment for another year did not result in any improvement in growth factor level either. The patient does not have the typical Laron craniofacial and somatic features.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Analysis of <jats:italic>GHR<\/jats:italic> showed a heterozygous nonsense mutation (c.703C&gt;T; p.Arg217X). Extensive mutation screening as well as copy number variation analysis of other candidate genes in the GH\u2010IGF\u2010I axis excluded any additional genetic defects. Analysis of the patient\u2019s fibroblasts showed that growth hormone receptor (GHR) messenger ribonucleic acid (mRNA) expressed from the mutant allele was degraded by a mechanism called nonsense\u2010mediated mRNA decay (NMD).<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> GHIS in this patient is because of a heterozygous nonsense mutation in <jats:italic>GHR<\/jats:italic>. Our study is the first to demonstrate that NMD is involved in the phenotypic variability of GHIS caused by <jats:italic>GHR<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2011.04304.x","type":"journal-article","created":{"date-parts":[[2011,11,25]],"date-time":"2011-11-25T11:30:15Z","timestamp":1322220615000},"page":"706-712","source":"Crossref","is-referenced-by-count":8,"title":["Growth hormone insensitivity syndrome caused by a heterozygous GHR mutation: phenotypic variability owing to moderation by nonsense\u2010mediated decay"],"prefix":"10.1111","volume":"76","author":[{"given":"Darya Gorbenko","family":"del Blanco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C. 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