title: Mutation analysis of the growth factor genes PlGF, Flt1, IGF-I, and IGF-IR in intrauterine growth restriction with abnormal placental blood flow.
abstract: OBJECTIVE
  The objective of our study was to investigate a possible role of pathogenic mutations in the growth factor genes insulin like growth factor I (IGF-I) and placental growth factor (PlGF) and their receptors IGF-IR and fms-like tyrosine kinase 1 (Flt1) in the pathogenesis of placental dysfunction.
  
  
  METHODS
  We analyzed two patient groups with IUGR (intrauterine growth restriction), 18 mother-child pairs with absent or reversed enddiastolic flow (ARED) in the umbilical artery and 12 mother-child pairs with preserved enddiastolic flow (PED) in the presence of a bilateral abnormal uterine artery Doppler waveform (Notching). The control group comprised of 50 healthy mother-child pairs.
  
  
  RESULTS
  Sequencing did not show a pathogenic mutation in any of the analyzed genes. However, we detected three novel polymorphisms in the IGF-IR gene. In addition, we identified one unknown polymorphism in exon 1 of the non-coding region of PlGF and 2 novel variants in exons 1 and 6 of Flt1.
  
  
  CONCLUSIONS
  In summary, our results do not provide evidence for a relevant role of pathogenic mutations in the genes IGF-I, IGF-IR, PlGF, and Flt1 in the etiology of IUGR with ARED or PED flow.
authors: Institute of Human Genetics, RWTH Aachen University Hospital, Aachen, Germany. smuetze@ukaachen.de
authors: Sabine
authors: S
authors: Muetze
authors: Athina
authors: A
authors: Kapagerof
authors: Lazaros
authors: L
authors: Vlachopoulos
authors: Thomas
authors: T
authors: Eggermann
authors: Peter
authors: P
authors: Kaufmann
authors: Klaus
authors: K
authors: Zerres
authors: Werner
authors: W
authors: Rath
authors: Sabine
authors: S
authors: Rudnik-Schoeneborn
mesh_terms: D001158:Arteries / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003971:Diastole; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D010920:Placenta / Q000098:blood supply*; D000072483:Placenta Growth Factor; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D014469:Umbilical Arteries / Q000503:physiopathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D007334:Insulin-Like Growth Factor I; C501162:FLT1 protein, human; D017526:Receptor, IGF Type 1; D040281:Vascular Endothelial Growth Factor Receptor-1