title: Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21).
abstract: OBJECTIVE
  Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies.
  
  
  METHODS
  Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls.
  
  
  RESULTS
  Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS.
  
  
  CONCLUSIONS
  miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS.
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany ; Research Center for Immune Science (RCIS), Charité University Medicine, Hessische Strasse 3-4, 10115 Berlin, Germany.
authors.forename: Julian
authors.identifier: 0000-0003-3169-3172
authors.initials: J
authors.lastname: Kamhieh-Milz
authors.affiliation: Institute for Human Genetics, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany ; Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Reham Fadl Hassan
authors.initials: RF
authors.lastname: Moftah
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Gürkan
authors.identifier: 0000-0003-0868-4059
authors.initials: G
authors.lastname: Bal
authors.affiliation: Systems Biology and Bioinformatics Laboratory, University of Algarve, Campus of Gambelas, 8005-139 Faro, Portugal.
authors.forename: Matthias
authors.identifier: 0000-0002-6245-8071
authors.initials: M
authors.lastname: Futschik
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Viktor
authors.identifier: 0000-0001-7915-224X
authors.initials: V
authors.lastname: Sterzer
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Omid
authors.identifier: 0000-0003-2124-4971
authors.initials: O
authors.lastname: Khorramshahi
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Burow
authors.affiliation: Human Genetics Practice, Friedrichstraße 147, 10117 Berlin, Germany.
authors.forename: Gundula
authors.initials: G
authors.lastname: Thiel
authors.affiliation: Human Genetics Practice, Friedrichstraße 147, 10117 Berlin, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Stuke-Sontheimer
authors.affiliation: Prenatal Diagnosis and Human Genetics Centre, Friedrichstraße 147, 10117 Berlin, Germany.
authors.forename: Rabih
authors.initials: R
authors.lastname: Chaoui
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Sundrela
authors.identifier: 0000-0002-9215-8598
authors.initials: S
authors.lastname: Kamhieh-Milz
authors.affiliation: Institute for Transfusion Medicine, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D004314:Down Syndrome / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D016212:Transforming Growth Factor beta / Q000235:genetics; D014314:Trisomy
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D016212:Transforming Growth Factor beta