{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T13:29:52Z","timestamp":1774790992301,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>The IGF\/IGF1R axis is involved in the regulation of human growth. Both IGF1 and IGF2 can bind to the IGF1R in order to promote growth via the downstream PI3K\/AKT pathway. Pathogenic mutations in <jats:italic>IGF1<\/jats:italic> and <jats:italic>IGF1R<\/jats:italic> determine intrauterine growth restriction and affect postnatal body growth. However, to date, there are only few reports of pathogenic <jats:italic>IGF2<\/jats:italic> mutations causing severe prenatal, as well as postnatal growth retardation.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Here we describe a <jats:italic>de novo<\/jats:italic> c.195delC <jats:italic>IGF2<\/jats:italic> variant (NM_000612, p.(Ile66Ser<jats:italic>fs<\/jats:italic>*93)) in a 4-year-old patient with severe pre- and post-natal growth retardation in combination with dystrophy, facial dimorphism, finger deformities, as well as a patent ductus. Cloning and sequencing of a long-range PCR product harboring the deletion and a SNP informative site chr11:2153634 (rs680, NC_000011.9:g.2153634T&gt;C) demonstrated that the variant resided on the paternal allele. This finding is consistent with the known maternal imprinting of <jats:italic>IGF2<\/jats:italic>. 3D protein structure prediction and overexpression studies demonstrated that the p.(Ile66Ser<jats:italic>fs<\/jats:italic>*93) <jats:italic>IGF2<\/jats:italic> gene variation resulted in an altered protein structure that impaired ligand\/receptor binding and thus prevents IGF1R activation.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The severity of the phenotype in combination with the dominant mode of transmission provides further evidence for the involvement of IGF2 in growth disorders.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-18-0601","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T16:15:01Z","timestamp":1539101701000},"page":"K1-K13","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":21,"title":["A new p.(Ile66Serfs*93) IGF2 variant is associated with pre- and postnatal growth retardation"],"prefix":"10.1093","volume":"180","author":[{"given":"Denise","family":"Rockstroh","sequence":"first","affiliation":[{"name":"1Department of Women and Child Health, University of Leipzig Hospitals and Clinics, Leipzig, Germany"},{"name":"2Center for Pediatric Research Leipzig, Department of Women\u2019s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Pf\u00e4ffle","sequence":"additional","affiliation":[{"name":"1Department of Women and Child Health, University of Leipzig Hospitals and Clinics, Leipzig, Germany"},{"name":"2Center for Pediatric Research Leipzig, Department of Women\u2019s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Le Duc","sequence":"additional","affiliation":[{"name":"3Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"R\u00f6\u00dfler","sequence":"additional","affiliation":[{"name":"3Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Schlensog-Schuster","sequence":"additional","affiliation":[{"name":"1Department of Women and Child Health, University of Leipzig Hospitals and Clinics, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T","family":"Heiker","sequence":"additional","affiliation":[{"name":"4Institute of Biochemistry, Faculty of Life Sciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Kratzsch","sequence":"additional","affiliation":[{"name":"5Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wieland","family":"Kiess","sequence":"additional","affiliation":[{"name":"1Department of Women and Child Health, University of Leipzig Hospitals and Clinics, Leipzig, Germany"},{"name":"2Center for Pediatric Research Leipzig, Department of Women\u2019s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes R","family":"Lemke","sequence":"additional","affiliation":[{"name":"3Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rami","family":"Abou Jamra","sequence":"additional","affiliation":[{"name":"3Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Pf\u00e4ffle","sequence":"additional","affiliation":[{"name":"1Department of Women and Child Health, University of Leipzig Hospitals and Clinics, Leipzig, Germany"},{"name":"2Center for Pediatric Research Leipzig, Department of Women\u2019s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/180\/1\/EJE-18-0601.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/180\/1\/EJE-18-0601.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:12:27Z","timestamp":1676391147000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/180\/1\/K1\/6654485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/eje-18-0601","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1]]}}}