title: Paternally Inherited IGF2 Mutation and Growth Restriction.
abstract: In humans, mutations in IGF1 or IGF1R cause intrauterine and postnatal growth restriction; however, data on mutations in IGF2, encoding insulin-like growth factor (IGF) II, are lacking. We report an IGF2 variant (c.191C→A, p.Ser64Ter) with evidence of pathogenicity in a multigenerational family with four members who have growth restriction. The phenotype affects only family members who have inherited the variant through paternal transmission, a finding that is consistent with the maternal imprinting status of IGF2. The severe growth restriction in affected family members suggests that IGF-II affects postnatal growth in addition to prenatal growth. Furthermore, the dysmorphic features of affected family members are consistent with a role of deficient IGF-II levels in the cause of the Silver-Russell syndrome. (Funded by Bundesministerium für Bildung und Forschung and the European Union.).
authors.affiliation: From the Institute of Human Genetics, University Hospital, Rhine-Westphalia Institute of Technology (RWTH) Aachen, Aachen (M.B., L.S., T.E.), Department of Pediatrics and Neuropediatrics, University Medicine, Göttingen, and Genetikum, Genetic Counseling and Diagnostics, Stuttgart (B.Z.), Ligandis, Gülzow-Prüzen (E.W.), Department of Pediatrics and Neuropediatrics, SLK-Kliniken, Heilbronn (H.-M.B.), and Pediatric Endocrinology Section, University Children's Hospital, University of Tübingen, Tübingen (R.S., G.B.) - all in Germany; and the Department of Clinical Genetics, Leiden University Medical Center (G.S.), GenomeScan (G.S., W.W.), and ServiceXS (W.W.) - all in Leiden, the Netherlands.
authors.forename: Matthias
authors.initials: M
authors.lastname: Begemann
authors.forename: Birgit
authors.initials: B
authors.lastname: Zirn
authors.forename: Gijs
authors.initials: G
authors.lastname: Santen
authors.forename: Elisa
authors.initials: E
authors.lastname: Wirthgen
authors.forename: Lukas
authors.initials: L
authors.lastname: Soellner
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Büttel
authors.forename: Roland
authors.initials: R
authors.lastname: Schweizer
authors.forename: Wilbert
authors.initials: W
authors.lastname: van Workum
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
mesh_terms: D018389:Codon, Nonsense; D005220:Fathers; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000172:deficiency / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D056730:Silver-Russell Syndrome / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II