The clinical implementation of non‐invasive prenatal diagnosis for single‐gene disorders: challenges and progress made

Abstract

Recently, we have witnessed the rapid translation into clinical practice of non-invasive prenatal testing for the common aneuploidies, most notably within the United States and China. This represents a lucrative market with testing being driven by companies developing and offering their services. These tests are currently aimed at women with high/medium-risk pregnancies identified by serum screening and/or ultrasound scanning. Uptake has been impressive, albeit limited to the commercial sector. However, non-invasive prenatal diagnosis (NIPD) for single-gene disorders has attracted less interest, no doubt because this represents a much smaller market opportunity and in the majority of cases has to be provided on a bespoke, patient or disease-specific basis. The methods and workflows are labour-intensive and not readily scalable. Nonetheless, there exists a significant need for NIPD of single-gene disorders, and the continuing advances in technology and data analysis should facilitate the expansion of the NIPD test repertoire. Here, we review the progress that has been made to date, the different methods and platform technologies, the technical challenges, and assess how new developments may be applied to extend testing to a wider range of genetic disorders.

An easy test but a hard decision: ethical issues concerning non-invasive prenatal testing for autosomal recessive disorders

“…4 As the discovery of cell-free fetal DNA in maternal blood is over 15 years ago, 5 the analysis of cell-free fetal DNA has been implemented for specific clinical applications such as fetal sex-determination to support the prenatal diagnosis of X-linked disorders 6 and fetal RhD status. 7 Research on the use of non-invasive prenatal diagnosis (NIPD) for the diagnosis of single gene disorders has to implementation for some conditions 8 and there is considerable support by prospective parents and health professionals for further development in this area. 9,10 European guidelines on the provision of prenatal-testing stress the need for prenatal testing to be offered without coercion, and also that provision of accurate, understandable information be provided to ensure a fully informed choice.…”

Offering prenatal diagnostic tests: European guidelines for clinical practice

“…19 According to a recent systematic review on the factors influencing the use of NIPT, 20 users and potential users cite the advantages of the non-invasive test as including earlier diagnosis (allowing earlier reassurance or decisions about the future of the pregnancy) and removal of the risk of fetal loss owing to the test. 21,22 However, the ease with which the test can be performed has made some women, health professionals and members of the general public concerned that parents might consent to the test without sufficient consideration of the consequences.…”

A „szabad” nukleinsavak jelentősége a noninvazív diagnosztikában

“…A téves pozitív eredmények 0,5% alatt vannak [31,32]. A legutóbbi eredmények alapján a módszer már alkalmas a magzati RhD vércsoport, a génmutációk, a nemikromoszóma-rendellenességek, microdeletiók, mikroduplikációk és egyéb kromoszómaeltérések kimutatására is [33]. A Magyar Humángenetikai Társaság állásfoglalását már 2014-ben megfogalmazta az eljárással kapcsolatban, a többi nemzetközi genetikai társasághoz hasonlóan.…”