Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21).

Julian Kamhieh-Milz,Rabih Chaoui,Abdulgabar Salama,Reham Fadl Hassan Moftah,Martin Burow,Gundula Thiel,Viktor Sterzer,Matthias Futschik,Sundrela Kamhieh-Milz,Omid Khorramshahi,Gürkan Bal,Annegret Stuke-Sontheimer

doi:10.1155/2014/402475

Abstract

Objectives. 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.

Highlights

Chromosomal aneuploidy is a main cause of human prenatal and postnatal morbidity and mortality and the main genetic cause of mental retardation
In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies
A wide range of organ systems are affected in Down syndrome individuals, with some being congenital whereas others are progressive, and include cardiac malformations, increased frequency of childhood leukemia, and varying degrees of mental retardation [27]. miRNAs are considered to play an active role in the regulation of developmental processes

Summary

Introduction

Chromosomal aneuploidy is a main cause of human prenatal and postnatal morbidity and mortality and the main genetic cause of mental retardation. The most common aneuploidy amongst live-borns is Trisomy 21, phenotypically manifested as Down syndrome (DS) [1]. Down syndrome occurs in approximately 1 in 700 live births worldwide, with the incidence rising with advanced maternal age [1]. Prenatal testing for trisomy’s is currently available to women of advanced maternal age, with ultrasound findings consistent with DS or with previous fetuses afflicted with chromosomal abnormalities [2]. A small but measurable risk of fetal loss is associated with prenatal diagnostic invasive procedures [3]. There exists a salient necessity to develop noninvasive aneuploidy screening tests with a high level of sensitivity and a negligible rate of false positives

Objectives

Methods

Results

Conclusion