InterGenetics presents the newly developed FetalSafe® genomic test, which analyzes rapidly, through massive parallel sequencing, the DNA of ~300 genes of the embryo. These carefully selected genes are associated with many severe genetic disorders, which may present in the newborn child.
It is estimated that about 1 in 50 newborn babies may be affected with a genetic disease, presenting with physical disabilities, malformations, and/or mental retardation. Most of these diseases are due to genetic defects, involving chromosomal abnormalities or gene mutations, i.e. abnormalities of the ‘human software’, and these may be either due to new mutations in the embryo or they may have been inherited from healthy and unsuspecting parents-carriers. Most of these genetic abnormalities may have quite serious effects on the quality of life of the affected infants.
Today, we have at our disposal the technological means of detecting these abnormalities before birth and therefore we should be able to propose preventive diagnostic strategies and, ideally, all pregnancies should be encouraged towards this approach.
Genomic testing for >95% of severe genetic disorders in the fetus
The FetalSafe® test is performed through a combination of two powerful diagnostic genetic methodologies:
- genomic testing through Next Generation Sequencing – NGS, which is in a position to detect all pathogenic mutations in 300 genes, associated with more than 350 serious genetic diseases
- prenatal molecular karyotype-aCGH, which affords the targeted detection of chromosomal imbalances in several hundred clinically important regions, leading to the diagnosis of more than 95% of recognized pathogenic chromosomal abnormalities.
This new test is based on DNA analysis of fetal cells, obtained in the 1st trimester of pregnancy through chorionic villi sampling (risk less than 1/300) or in the 2nd trimester through amnioticentesis (risk less than 1/1,000).
Furthermore, the test is completed within 7 days, minimizing parental anxiety.
This is a diagnostic test, in contrast to other prenatal tests which are based on statistical risks and are not fully diagnostic.
The test is aimed at parents who wish the most comprehensive preventive testing for genetic disorders which may affect their newborn child
The FetalSafe® test detects pathologenic mutations 300 genes (see list of genes), offering a diagnosis for many serious hereditary disorders, such as:
- cystic fibrosis,
- common hearing-loss disorders
- approximately 170 neurogenetic diseases
- a large number of retinopathies
- 22 metabolic diseases, and
- more than 90 severe pediatric disorders, such as Noonan syndrome, Smith-Lemli-Opitz syndrome, Treacher-Collins syndrome, polycystic kidney disease-infantile, osteogenesis imperfecta, etc.
- other serious genetic diseases which may appear later in life, such as Marfan syndrome, neurofibromatosis, polycystic kidney disease-adult, etc.
The number of genes and the corresponding genetic disorders may be updated and expanded depending on new scientific knowledge.
In parallel with the aforementioned gene defects,the application of prenatal molecular karytype may also accurately diagnose chromosomal abnormalities, such as Down syndrome (trisomy 21) and numerous other sub-microscopic abnormalities involving small chromosomal regions that are deleted or duplicated and which are not detectable by conventional karyotype analysis.
The abnormalities revealed by prenatal molecular karyotype are associated with hundreds of known genetic diseases and syndromes, which present with various congenital malformations and/or intellectual disability/developmental delay.
Testing requires a biological sample from the fetus, such as chorionic villi or amniotic fluid. Prior to testing, the parents must complete and sign the Patient Consent Form, after receiving mandatory pre-test genetic counseling.
The sample is shipped to our laboratory where genomic DNA is extracted, followed by exome enrichment for the ~300 genes and massive parallel sequencing (also known as Next Generation Sequencing – NGS). Sequence reads are then aligned and mapped to the human genome reference sequence and all variants and putative mutations are prioritized through a proprietary in-house bioinformatics pipeline.
Only known or obligatory pathogenic mutations will be reported, together with a full clinical assessment and clinical genetic evaluation
It is therefore clear that this test includes a very large number of genetic diseases and has the great advantage that it leads to a definitive diagnosis, as it is not based on statistical risk assessments which leave uncertainties, as is the case with non-invasive prenatal diagnosis from maternal blood (NIPT).
In cases with positive findings, the couple shall be notified that the results will be communicated through an obligatory (online) genetic counseling session.
Please note that the test also includes MLPA analysis for the detection of deletions/duplications of the SMN1 gene and the DMD gene (in male fetuses only), associated with the genetic disorders Spinal Muscular Atrophy ‐ SMA (OMIM 253300) and Duchenne/Becker muscular dystrophy (DMD/BMD ‐ OMIM 310200). In male fetuses only we also include testing for Fragile X syndrome.
The test is highly sensitive and complex, so it is necessary that the results are assessed by a specialized team of clinical and molecular geneticists, in order to ensure safe and reliable testing.
Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.
Parents who have chosen the FetalSafe® test feel reassured and relieved that they have excluded most serious genetic diseases which could occur in their child
Results are evaluated and reported based on current knowledge.
The applied methodology may not necessarily detect all the possible pathogenic mutations of each gene/disease. Generally, the analysis covers a large percentage (~95%) of mutations in exons-coding regions of the genes, while it does not generally detect mutations in non-coding regions/introns and exonic deletions or duplications >15-20 base-pairs.
Therefore, a negative result does not exclude totally the presence of a pathogenic mutation in the embryo.