Prenatal maternal plasma DNA screening for cystic fibrosis: A

Prenatal cystic fibrosis (CF) screening is currently based on Background: determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. The method relies on the quantitative amplification of the CF gene to Methods: determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. The estimated detection rate (sensitivity) is 70% (100% of those Results: detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Compared with current screening practice based on parental Conclusions: carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study. Nicholas J. Wald ( ) Corresponding author: [email protected] : Conceptualization, Formal Analysis, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing; Author roles: Old RW : Conceptualization, Formal Analysis, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing; : Bestwick JP Wald NJ Conceptualization, Formal Analysis, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Robert Old has applied for a UK patent (application nos. 1619812.9 and 1702924.0 priority date 23 November 2016) for the Competing interests: method described in this paper and assigned the invention to Logical Medical Systems, of which Nicholas Wald is a Director. Old RW, Bestwick JP and Wald NJ. How to cite this article: Prenatal maternal plasma DNA screening for cystic fibrosis: A computer 2017, :1896 (doi: modelling study of screening performance [version 1; referees: 1 approved] F1000Research 6 ) 10.12688/f1000research.12849.1 © 2017 Old RW . This is an open access article distributed under the terms of the , which Copyright: et al Creative Commons Attribution Licence permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) declared that no grants were involved in supporting this work. Grant information: 27 Oct 2017, :1896 (doi: ) First published: 6 10.12688/f1000research.12849.1 Referee Status: