A New Homozygous IGF1R Variant Defines a Clinically Recognizable Incomplete Dominant form of SHORT Syndrome

Paolo Prontera, Lucia Micale, Alberto Verrotti, Valerio Napolioni, Gabriela Stangoni, Giuseppe Merla

Research output: Contribution to journalArticlepeer-review

Abstract

Here, we describe a child, born from consanguineous parents, with clinical features of SHORT syndrome, high IGF1 levels, developmental delay, CNS defects, and marked progeroid appearance. By exome sequencing, we identified a new homozygous c.2201G>T missense mutation in the IGF1R gene. Proband's parents and other relatives, all heterozygous carriers of the mutation, presented with milder phenotype including high IGFI levels, short stature, and type 2 diabetes. Functional studies using patient's cell lines showed a lower IGF1R expression that leads to the alteration of IGF1R-mediated PI3K/AKT/mTOR downstream pathways, including autophagy. This study defines a clinically recognizable incomplete dominant form of SHORT syndrome, and provides relevant insights into the pathophysiological and phenotypical consequences of IGF1R mutations.

Original languageEnglish
Pages (from-to)1043-1047
Number of pages5
JournalHuman Mutation
Volume36
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Keywords

  • IGF1
  • IGF1R
  • Neonatal progeroid syndrome
  • PI3K
  • SHORT syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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