title: Improved prenatal detection of a fetal point mutation for achondroplasia by the use of size-fractionated circulatory DNA in maternal plasma--case report.
abstract: BACKGROUND
  The efficacious analysis of fetal loci involving point mutations from circulatory fetal DNA in maternal plasma is hindered by the preponderance of maternal DNA. It has recently been shown that the size difference between fetal and maternal DNA species can be used for the selective enrichment of circulatory fetal DNA in maternal plasma. We have now tested this approach for the detection of a fetal point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia.
  
  
  METHODS
  Circulatory DNA was extracted from maternal plasma and size-fractionated by agarose gel electrophoresis. The fraction with a size less than 300 bp was examined by a touchdown PCR assay specific for the FGFR3 gene, and the mutation was identified by SfcI restriction analysis.
  
  
  RESULTS
  Our analysis indicated that although the fetal mutation was discernible in the analysis of total plasma DNA, the result using size-fractionated DNA was much more evident.
  
  
  CONCLUSIONS
  The enrichment of circulatory fetal DNA in maternal plasma by size-fractionation facilitates the detection of subtle feto-maternal genetic differences, such as those involving point mutations. This approach can easily be extended for the non-invasive prenatal determination of other fetal loci.
authors.affiliation: Laboratory for Prenatal Medicine, University Women's Hospital/Department of Research, Basel, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Holzgreve
authors.forename: G C M L
authors.initials: GC
authors.lastname: Page-Christiaens
authors.forename: J J P
authors.initials: JJ
authors.lastname: Gille
authors.forename: S
authors.initials: S
authors.lastname: Hahn
mesh_terms: D000130:Achondroplasia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000649:Amniocentesis; D004247:DNA / Q000032:analysis / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D005333:Fetus / Q000166:cytology*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011296:Prenatal Diagnosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D004247:DNA; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3