To date, no prenatal screening tests can provide information comparable in reliability and completeness to those that can be obtained from the examination of fetal material obtained by CVS or amniotic fluid and the subsequent genomic study offered by NGPD.
The objective is to link the progress achieved in the field of obstetrics and gynecology (with a risk of miscarriage following an amniocentesis which is almost comparable to a natural prgnancy) to what has been achieved in the field of diagnostics. Thanks to the use of more accurate techniques, such as Next Generation Sequencing (NGS), it is potentially possible to sequence the entire human genome in a few days (for the Human Genome Project, the older technology took more than ten years to produce the first sequences). In the field of genetic diagnosis, the NGS enables the simultaneous analysis of hundreds of genes in their entire sequence rapidly and therefore compatible with the timing of prenatal diagnosis.
Through the use of sophisticated tools (MiSeq, NextSeq500) and the use of suitable work flow in order to process the data obtained, there is a now a “panel of genes,” or library, associated with about 100 diseases selected according frequency within the population (see Table B). For these genes, there will be an exclusion of correlated pathologies related to hereditary mutations and for random ones (de novo) known in tliterature and of clear clinical significance (about 7000 pathogenic mutations will be searched for).
Apart from cytogenetic karyotype analysis (see Table A), NPGD also includes chromosome analysis by array-CGH. With this technique, it is possible n a few days to analyze microdeletion and microduplication pathologies (see Tab C), which are not detectable by conventional karyotyping, because all chromosomes can be analysed at a higher resolution. Some diseases have yet to be analyzed by NGS due to the type of molecular variation which influence them (dystrophy, Becker muscular dystrophy, fragile X and SMA). For the diagnosis of these diseases, genetic methodologies are considered the gold standard.
In conclusion, to date, NGPD is the only technique able to guaranteeabsolute results quickly providing the maximum amount of information possible on the state of health of the fetus. A negative result obtained with the NGPD would reduce all other forms of prenatal investigation to a role of secondary importance.
Although, as mentioned on numerous occasions, the study of the fetal karyotype and the modern techniques of molecular cytogenetics (array-CGH) and molecular biology (Next Generation Sequencing) cannot guarantee with absolute certainty that the fetus is healthy, NGPD reduces of the risk of failing to identify a genetic disorder more than any other prenatal investigation has been able to do to date.
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The most frequent genetic abnormalities will be investigated and excluded, and any changes identified will be evaluated and discussed in the genetic counseling to pregnant women. The remaining possibility of having a child with genetic problems is linked to rare forms of the disease and multi-factorial defects which sometimes cannot be identified with any certainty even after birth.
