Non‐invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next‐generation sequencing allows for a safer, more accurate, and comprehensive approach. (26th May 2015)

• Record Type: Journal Article
• Authors: Chitty, Lyn S.; Mason, Sarah; Barrett, Angela N.; McKay, Fiona; Lench, Nicholas; Daley, Rebecca; Jenkins, Lucy A.
• Is Part Of: Prenatal diagnosis. Volume 35:Number 7(2015:Jul.)
• Page Start: 656
• Page End: 662
• Publication Date: 2015-05-26
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4583
• Languages: English
• ISSNs: 0197-3851

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="pd4583-sec-0034" sec-type="section"> <title>Objective</title> <p>Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next‐generation sequencing (NGS) for the analysis of cell‐free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders.</p> </sec> <sec id="pd4583-sec-0035" sec-type="section"> <title>Methods</title> <p>Analysis of cell‐free DNA using a PCR and restriction enzyme digest (PCR–RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia.</p> </sec> <sec id="pd4583-sec-0036" sec-type="section"> <title>Results</title> <p>PCR–RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR–RED.</p> </sec> <sec id="pd4583-sec-0037" sec-type="section"> <title>Conclusion</title> <p>NGS provides an accurate, flexible approach to non‐invasive prenatal diagnosis of <italic>de novo</italic> and paternally inherited mutations. It is more sensitive than PCR–RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non‐invasive prenatal diagnosis for other monogenic disorders. © 2015 John Wiley & Sons, Ltd.</p> </sec> </abstract>