title: An insulin-like growth factor-I receptor defect associated with short stature and impaired carbohydrate homeostasis in an Italian pedigree.
abstract: BACKGROUND
  Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis.
  
  
  METHODS
  We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts.
  
  
  RESULTS
  All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between -1.65 and -2.37 and birth length SDS between -1.78 and -3.08. Their postnatal growth was also impaired, with height SDS between -1.75 and -4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case's sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity.
  
  
  CONCLUSIONS
  This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism.
authors.affiliation: Department of Pediatrics, University of Chieti, Chieti, Italy. amohn@unich.it
authors.forename: A
authors.initials: A
authors.lastname: Mohn
authors.forename: M L
authors.initials: ML
authors.lastname: Marcovecchio
authors.forename: T
authors.initials: T
authors.lastname: de Giorgis
authors.forename: R
authors.initials: R
authors.lastname: Pfaeffle
authors.forename: F
authors.initials: F
authors.lastname: Chiarelli
authors.forename: W
authors.initials: W
authors.lastname: Kiess
mesh_terms: D000293:Adolescent; D000328:Adult; D000365:Age Determination by Skeleton; D001724:Birth Weight / Q000235:genetics; D050260:Carbohydrate Metabolism / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D017526:Receptor, IGF Type 1