Paternally Inherited IGF2 Mutation and Growth Restriction

N Engl J Med. 2015 Jul 23;373(4):349-56. doi: 10.1056/NEJMoa1415227. Epub 2015 Jul 8.

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.).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon, Nonsense*
  • Fathers
  • Female
  • Fetal Growth Retardation / genetics
  • Growth Disorders / genetics*
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor II / deficiency
  • Insulin-Like Growth Factor II / genetics*
  • Male
  • Pedigree
  • Phenotype
  • Silver-Russell Syndrome / genetics*

Substances

  • Codon, Nonsense
  • IGF2 protein, human
  • Insulin-Like Growth Factor II