{"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":1789989894276,"version":"4.0.1"},"reference-count":0,"publisher":"Bioscientifica","issue":"6","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>\n                    Mutation in the insulin-like growth factor-1 receptor (\n                    <jats:italic>IGF1R<\/jats:italic>\n                    ) gene is a rare cause for intrauterine and postnatal growth disorders. Patients identified with\n                    <jats:italic>IGF1R<\/jats:italic>\n                    mutations present with either normal or impaired glucose tolerance. None of the cases described so far showed hypoglycemia. We aimed to identify the genetic basis for small for gestational age, short stature and hypoglycemia over three generations in one family. The proband, a 9-year-old male, presented in infancy with recurrent hypoglycemic episodes, symmetric intrauterine growth retardation and postnatal growth retardation. Blood DNA samples from the patient, his parents, a maternal sister and maternal grandmother underwent Sanger sequencing of the\n                    <jats:italic>IGF1R<\/jats:italic>\n                    gene. Primary skin fibroblast cultures of the patient, his mother and age- and sex-matched control donors were used for gene expression and receptor functional analyses. We found a novel heterozygous mutation (c.94\u2009+\u20091g\u2009&gt;\u2009a, D1105E) affecting the splicing site of the\n                    <jats:italic>IGF1R<\/jats:italic>\n                    mRNA in the patient, his mother and his grandmother. Primary fibroblast cultures derived from the patient and his mother showed reduced proliferation and impaired activation of the IGF1R, evident by reduced IGF1R and AKT phosphorylation upon ligand binding. In conclusion, the newly identified heterozygous missense mutation in exon 1 of\n                    <jats:italic>IGF1R<\/jats:italic>\n                    (D1105E) results in impaired IGF1R function and is associated with small for gestational age, microcephaly and abnormal glucose metabolism. Further studies are required to understand the mechanisms by which this mutation leads to hypoglycemia.\n                  <\/jats:p>","DOI":"10.1530\/ec-17-0038","type":"journal-article","created":{"date-parts":[[2017,6,25]],"date-time":"2017-06-25T20:10:15Z","timestamp":1498421415000},"page":"395-403","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":24,"title":["A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia"],"prefix":"10.1530","volume":"6","author":[{"given":"R","family":"Solomon-Zemler","sequence":"first","affiliation":[{"name":"1Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Basel-Vanagaite","sequence":"additional","affiliation":[{"name":"1Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel"},{"name":"2Raphael Recanati Genetic InstituteRabin Medical Center \u2013 Beilinson Hospital, Petach Tikva, Israel"},{"name":"3Felsenstein Medical Research CenterPetach Tikva, Israel"},{"name":"4Pediatric GeneticsSchneider Children\u2019s Medical Center of Israel, Petach Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Steier","sequence":"additional","affiliation":[{"name":"5Day Hospitalization DepartmentSchneider Children\u2019s Medical Center of Israel, Petach Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Yakar","sequence":"additional","affiliation":[{"name":"6David B. Kriser Dental CenterDepartment of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Mel","sequence":"additional","affiliation":[{"name":"7Jesse Z. and Sara Lea Shafer Institute for Endocrinology and DiabetesSchneider Children\u2019s Medical Center of Israel, Petach Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Phillip","sequence":"additional","affiliation":[{"name":"1Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel"},{"name":"7Jesse Z. and Sara Lea Shafer Institute for Endocrinology and DiabetesSchneider Children\u2019s Medical Center of Israel, Petach Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Bazak","sequence":"additional","affiliation":[{"name":"2Raphael Recanati Genetic InstituteRabin Medical Center \u2013 Beilinson Hospital, Petach Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Bercovich","sequence":"additional","affiliation":[{"name":"8Tel-Hai CollegeTel-Hai, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Werner","sequence":"additional","affiliation":[{"name":"1Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel"},{"name":"9Shalom and VardaYoran Institute for Human Genome ResearchTel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"de Vries","sequence":"additional","affiliation":[{"name":"1Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel"},{"name":"7Jesse Z. and Sara Lea Shafer Institute for Endocrinology and DiabetesSchneider Children\u2019s Medical Center of Israel, Petach Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/6\/6\/395.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/6\/6\/395.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:42:12Z","timestamp":1784554932000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/6\/6\/395-403\/35265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/ec-17-0038","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8]]}}}