{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:18Z","timestamp":1784557038212,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The homozygous GH receptor (\n                      <jats:italic>GHR<\/jats:italic>\n                      ) pseudoexon (6\u03a8) mutation leads to growth hormone insensitivity (GHI) with clinical and biochemical heterogeneity. We investigated whether transcript heterogeneity (6\u03a8-\n                      <jats:italic>GHR<\/jats:italic>\n                      to WT\n                      <jats:italic>-GHR<\/jats:italic>\n                      transcript ratio) and\/or concurrent defects in other short stature (SS) genes contribute to this.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      6\u03a8-\n                      <jats:italic>GHR<\/jats:italic>\n                      and WT\n                      <jats:italic>-GHR<\/jats:italic>\n                      mRNA transcripts of four 6\u03a8 patients (height SDS \u22124.2 to \u22123.1) and one control fibroblast were investigated by RT-PCR. Transcripts were quantified by qRT-PCR and delta delta CT analysis and compared using ANOVA with Bonferroni correction. In eleven 6\u03a8 patients, 40 genes known to cause GHI\/SS were analysed by targeted next generation sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RT-PCR confirmed 6\u03a8-\n                      <jats:italic>GHR<\/jats:italic>\n                      transcript in the 6\u03a8 patients but not in the control. 6\u03a8-\n                      <jats:italic>GHR<\/jats:italic>\n                      transcript levels were comparable in patients 1 and 3 but significantly different among all other patients. The mean 6\u03a8:WT transcript ratios ranged from 29\u201371:1 for patients 1\u20134 and correlated negatively with height SDS (R\u2009=\u2009\u22120.85;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Eight deleterious variants in six genes were detected, but the number of gene hits did not correlate with the degree of SS in individual 6\u03a8 patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Variable amounts of 6\u03a8- and WT-\n                      <jats:italic>GHR<\/jats:italic>\n                      transcripts were identified in 6\u03a8 patients but no 6\u03a8 transcript was present in the control. Higher 6\u03a8:WT\n                      <jats:italic>-GHR<\/jats:italic>\n                      transcript ratio correlated with SS severity and may explain the phenotypic variability. Analysis of known SS genes suggested that phenotypic variation is independent of the genetic background. This is the first report of transcript heterogeneity producing a spectrum of clinical phenotypes in different individuals harbouring an identical homozygous genetic mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-20-0026","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T14:06:56Z","timestamp":1581516416000},"page":"211-222","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":5,"title":["GHR gene transcript heterogeneity may explain phenotypic variability in GHR pseudoexon (6\u03a8) patients"],"prefix":"10.1530","volume":"9","author":[{"given":"Sumana","family":"Chatterjee","sequence":"first","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Cottrell","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Rose","sequence":"additional","affiliation":[{"name":"2Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talat","family":"Mushtaq","sequence":"additional","affiliation":[{"name":"3The Leeds Teaching Hospital NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinaash V","family":"Maharaj","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Williams","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin O","family":"Savage","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A","family":"Metherell","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen L","family":"Storr","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/9\/3\/EC-20-0026.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/9\/3\/EC-20-0026.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:43:54Z","timestamp":1784555034000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/9\/3\/211-222\/646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/ec-20-0026","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]}}}