Introducing the next generation sequencing in genomic amnio and villuos sampling. The so called "Next Generation Prenatal Diagnosis" (NGPD).

Abstract

In the last 30 years, invasive prenatal diagnosis has predominantly involved research into chromosomal anomalies, in particular Down’s Syndrome (1). In the last 10 years, parents have been requesting ever more information during pregnancy (2,3) and there has been an increase in the number of cases with ultrasound markers concerning possible fetal complications of unknown origin. This has led to the introduction of prenatal diagnosis and increasingly detailed techniques such as CGH Array (4-6). These techniques have become standard diagnostic practice in cases where the ultrasound scan provides a conflicting result. However, in reality, such procedures are thought to cover only 10% of the fetal anomalies linked to genetic malformations discovered at birth (7). Prenatal diagnosis is becoming more and more detailed due to the continual legal action taken by parents regarding diagnostic ultrasound which fails to identify fetal anomalies and regarding unwanted births in general (8-10). In fact, the continuous evolution of human genetics has led to the development of extremely detailed methodologies, which are able to evaluate not only the errors in chromosomes, both “big errors” (karyotype) and “small errors” (microdeletions, microduplications), but also gene mutations. To date, approximately 19,000 coding genes contained in the human exome have been identified. The recent introduction of NGS (Next Generation Sequencing) has made it possible, in theory, to explore the entire exome and reveal every form of mutation (11-15). Therefore, it is possible, today, to open up a completely new diagnostic scenario which would have been considered impossible only a few years ago. However, if this development is not controlled, it could lead to a so-called genetic “deviation”, i.e. a genetics that could have unforeseen repercussions on the life and dignity of the individual. In fact, the risks concerning possible social, emotional and financial consequences in the family and individual is very high. The potential negative impact of prenatal genetic testing must respect the “right not to know”. The exaggeration in ever more detailed testing concerning the genetic structure of the embryo creates tension within a family. In the future, this could create genetic discrimination regarding employment or health insurance costs (16,17). Despite the fact there is theoretically no technical limit to these methodologies, it is important to establish ethical and moral guidelines, at least regarding how these new methodologies are used in prenatal diagnosis.