title: Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations.
abstract: BACKGROUND
  Heterozygous mutations in the IGF1 receptor (IGF1R) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure. To date, homozygous mutations of this receptor have not been described.
  
  
  METHODS
  A 13.5-year-old girl born from healthy first-cousin parents presented with severe IUGR and persistent short stature. Mild intellectual impairment, dysmorphic features, acanthosis nigricans, and cardiac malformations were also present.
  
  
  METHODS
  Auxological and endocrinological profiles were measured. All coding regions of the IGF1R gene including intron boundaries were amplified and directly sequenced. Functional characterization was performed by immunoblotting using patient's fibroblasts.
  
  
  RESULTS
  IGF1 level was elevated at 950NG/ML (+7 S.D.). Fasting glucose level was normal associated with high insulin levels at baseline and during an oral glucose tolerance test. Fasting triglyceride levels were elevated. sequencing of the IGF1R gene led to the identification of a homozygous variation in exon 2: c.119G>T (p.Arg10Leu). As a consequence, IGF1-dependent receptor autophosphorylation and downstream signaling were reduced in patient's fibroblasts. Both parents were heterozygous for the mutation.
  
  
  CONCLUSIONS
  The homozygous mutation of the IGF1R is associated with severe IUGR, dysmorphic features, and insulin resistance, while both parents were asymptomatic heterozygous carriers of the same mutation.
authors.affiliation: Service d'Endocrinologie, Hôtel-Dieu de France Hospital, Beirut, Lebanon.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Gannagé-Yared
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.forename: Sandra
authors.initials: S
authors.lastname: Corbani
authors.forename: Hala
authors.initials: H
authors.lastname: Mégarbané
authors.forename: Joelle
authors.initials: J
authors.lastname: Abou Ghoch
authors.forename: Nancy
authors.initials: N
authors.lastname: Choucair
authors.forename: Roland
authors.initials: R
authors.lastname: Pfäffle
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D002675:Child, Preschool; D005183:Failure to Thrive / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics; D008958:Models, Molecular; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: D017526:Receptor, IGF Type 1