{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:10:31Z","timestamp":1793157031518,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Heterozygous mutations in the IGF1 receptor (<jats:italic>IGF1R<\/jats:italic>) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure. To date, homozygous mutations of this receptor have not been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subject<\/jats:title><jats:p>A 13.5-year-old girl born from healthy first-cousin parents presented with severe IUGR and persistent short stature. Mild intellectual impairment, dysmorphic features, acanthosis nigricans, and cardiac malformations were also present.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Auxological and endocrinological profiles were measured. All coding regions of the<jats:italic>IGF1R<\/jats:italic>gene including intron boundaries were amplified and directly sequenced. Functional characterization was performed by immunoblotting using patient's fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IGF1 level was elevated at 950\u200ang\/ml (+7<jats:sc>s.d<\/jats:sc>.). Fasting glucose level was normal associated with high insulin levels at baseline and during an oral glucose tolerance test. Fasting triglyceride levels were elevated. Sequencing of the<jats:italic>IGF1R<\/jats:italic>gene led to the identification of a homozygous variation in exon 2: c.119G&gt;T (p.Arg10Leu). As a consequence, IGF1-dependent receptor autophosphorylation and downstream signaling were reduced in patient's fibroblasts. Both parents were heterozygous for the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The homozygous mutation of the<jats:italic>IGF1R<\/jats:italic>is associated with severe IUGR, dysmorphic features, and insulin resistance, while both parents were asymptomatic heterozygous carriers of the same mutation.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-12-0701","type":"journal-article","created":{"date-parts":[[2012,10,9]],"date-time":"2012-10-09T05:20:28Z","timestamp":1349760028000},"page":"K1-K7","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":52,"title":["Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations"],"prefix":"10.1093","volume":"168","author":[{"given":"Marie-H\u00e9l\u00e8ne","family":"Gannag\u00e9-Yared","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Klammt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Chouery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Corbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"M\u00e9garban\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Abou Ghoch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Choucair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Pf\u00e4ffle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"M\u00e9garban\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"3","key":"1_23463112","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1210\/jc.2006-2017","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology &amp; 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