{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:24:54Z","timestamp":1789989894341,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T00:00:00Z","timestamp":1431302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"JSPS KAKENHI","award":["22790982"],"award-info":[{"award-number":["22790982"]}]},{"name":"JSPS KAKENHI","award":["20403412"],"award-info":[{"award-number":["20403412"]}]},{"name":"JSPS KAKENHI","award":["24591512"],"award-info":[{"award-number":["24591512"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The type I insulin\u2010like growth factor I receptor (IGF1R) plays an important role in growth. We aimed to evaluate the detailed mechanism underlying the effect of IGF1R on human growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>We have performed sequence analysis of <jats:italic>IGF1R<\/jats:italic> in 55 patients with <jats:styled-content style=\"fixed-case\">SGA<\/jats:styled-content> short stature in Japan, since 2004, and identified novel heterozygous nonsense mutations in 2 patients: an 8\u2010year\u2010old Japanese boy (case 1), with a birthweight of 2228\u00a0g (\u22123\u00b73 <jats:styled-content style=\"fixed-case\">SDS<\/jats:styled-content>) and height of 46\u00a0cm (\u22122\u00b71 <jats:styled-content style=\"fixed-case\">SDS<\/jats:styled-content>), and a 3\u2010year\u2010old Japanese girl (case 2), with a birthweight of 2110\u00a0g (\u22123\u00b70 <jats:styled-content style=\"fixed-case\">SDS<\/jats:styled-content>) and height of 44\u00b73\u00a0cm (\u22122\u00b78 <jats:styled-content style=\"fixed-case\">SDS<\/jats:styled-content>). Both patients had a short stature (\u22123\u00b72 SDS, \u22123\u00b71 <jats:styled-content style=\"fixed-case\">SDS<\/jats:styled-content>). We determined the protein expression of mutated <jats:italic><jats:styled-content style=\"fixed-case\">IGF1R<\/jats:styled-content>,<\/jats:italic> assessed the effect of the endoplasmic reticulum\u2010associated degradation (<jats:styled-content style=\"fixed-case\">ERAD<\/jats:styled-content>) pathway on mutated <jats:italic><jats:styled-content style=\"fixed-case\">IGF1R<\/jats:styled-content><\/jats:italic>, assessed the dominant\u2010negative effect of <jats:italic><jats:styled-content style=\"fixed-case\">IGF1R<\/jats:styled-content><\/jats:italic> and performed quantitative <jats:styled-content style=\"fixed-case\">RT\u2010PCR<\/jats:styled-content> analysis of <jats:italic><jats:styled-content style=\"fixed-case\">IGF1R<\/jats:styled-content><\/jats:italic> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression in whole blood cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel heterozygous nonsense mutations (case 1: p.Q1250X and case 2: p.W1249X) were identified. Although these mutations did not affect blood <jats:italic><jats:styled-content style=\"fixed-case\">IGF1R<\/jats:styled-content><\/jats:italic> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels, they significantly decreased the expression of IGF1R protein in transiently transfected cells. Treatment with the proteasome inhibitor <jats:styled-content style=\"fixed-case\">MG<\/jats:styled-content>132 showed significantly increased IGF1R protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Heterozygous nonsense mutations affecting the C\u2010terminal region (p.Q1250X, p.W1249X) of <jats:italic>IGF1R<\/jats:italic> decreased the expression of IGF1R through the <jats:styled-content style=\"fixed-case\">ERAD<\/jats:styled-content> pathway. Our study revealed the importance of the C\u2010terminal region and the dosage of this receptor for growth.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12791","type":"journal-article","created":{"date-parts":[[2015,4,10]],"date-time":"2015-04-10T23:16:38Z","timestamp":1428707798000},"page":"834-841","source":"Crossref","is-referenced-by-count":21,"title":["Heterozygous nonsense mutations near the C\u2010terminal region of IGF1R in two patients with small\u2010for\u2010gestational\u2010age\u2010related short stature"],"prefix":"10.1111","volume":"83","author":[{"given":"Masanobu","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Division of Pediatrics &amp; Perinatology Tottori University Faculty of Medicine Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kawashima Sonoyama","sequence":"additional","affiliation":[{"name":"Division of Pediatrics &amp; Perinatology Tottori University Faculty of Medicine Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Hamajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya City West Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Hamajima","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Metabolism Aichi Children's Health and Medical Center Obu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Kumura","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics Research Center for Bioscience and Technology Tottori University Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Division of Pediatrics &amp; 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