A Pre-conceptual Advanced Mutation Carrier Screening

A genetic test for single gene disorders utilizing Next Generation Sequencing (NGS)

Science Labs, in collaboration with SOPHiA GENETICS®, the Global Leader in Data-Driven Medicine, is the first and only genetic diagnostics center in Greece to implement the newly developed genetic test: PreDNA Test. This novel, innovative analysis allows for the thorough and detailed investigation of 569 human genes, which are related to more than 300 genetic disorders.

If all known Mendelian recessive genetic diseases are taken into consideration individually, their prevalence seems to be relatively low to cause any special concerns, except for some specific ones such as Thalassaemias, Cystic Fibrosis, Deafness, SMA etc. On the other hand their combined overall prevalence appears to affect a substantial proportion of our population. According to WHO (World Health Organization), the overall frequency of this type of diseases is 1% in newborns, worldwide. Moreover, hereditary diseases are causative for 20% of fetal mortality and approximately 18% of childhood morbidity, while recent publications show that more than half of future parents are mutation carriers of a (severe or less severe) recessively inherited genetic condition.
Moreover, there are many cases where a patient receives a diagnosis linked to a hereditary disorder, based on clinical criteria and perhaps different types of lab and/or imaging testing. However, the genetic cause is not defined, meaning that causative genetic alterations (mutations) as well as the related gene(s) are not determined. Without this knowledge, in some cases, the identification of other high risk family members and effective family planning are not feasible.
Science Labs, in collaboration with SOPHiA GENETICS®, has developed a molecular genetics mutation carrier test, recommended to be applied prior to a spontaneous or IVF pregnancy (preconception), which may reveal the probability of a couple giving birth to a severely affected child. If the test comes out positive, appropriate actions may be taken in favor of baring a healthy child.

• It may reveal cases where both future parents are mutation carriers, giving the option to prevent severe genetic disorders in their offspring.
• If both parents are carriers for a pathogenic mutation in the same gene, they have a high risk of having an affected child. In such situations, first or second trimester prenatal diagnosis following chorionic villus sampling (CVS) or amniocentesis respectively, may be an option. Moreover, there are other alternatives towards the direction of avoiding having an affected child, such as preimplantation genetic diagnosis (PGD) or the choice of a sperm/oocyte donor prior to in vitro fertilization (IVF).
In only one single test, it investigates, in parallel, 569 genes related to more than 300 genetic disorders. Thus, an extended mutation carrier investigation is performed, in a shorter turn-around-time and at a lower cost compared to single gene testing, which testing wouldn’t be feasible in a single diagnostic lab.

Every future parent may undergo this testing and so can sperm/oocyte donors, aiming to participate in IVF programs, thus reducing the chance of giving birth to a child affected by a hereditary condition.

International studies have shown that >5% of couples have a high risk of having a child presenting genetic abnormalities such as:
• Thalassemias (carrier frequency 1 in 12)
• Cystic Fibrosis (carrier frequency 1 in 25)
• Spinal Muscular Atrophy-SMA (carrier frequency 1 in 50)
• Polycystic Kidney Disease-PKD (carrier frequency 1 in 70)
• Non-syndromic Hearing Impairment (carrier frequency 1 in 80)
• Mucopolysaccharidosis (carrier frequency 1 in 80)
• Gaucher disease (carrier frequency 1 in 200)
• Fragile X syndrome (carrier frequency 1 in 250)
• Retinitis Pigmentosa
• Intellectual disabilities
• Autism spectrum and others

The method implemented is based on cutting-edge technology. The gene panel, designed in collaboration with SOPHiA GENETICS®, exploits the capture target enrichment method and Illumina Next Generation Sequencing technology (NextSeq-500).
In detail: 1. Regions investigated are selected, libraries are constructed and QC metrics are obtained in different steps. 2. Next Generation Sequencing is subsequently performed on an Illumina NextSeq-500 NGS sequencer. 3. Using the Sophia DDM® SaaS Analytics platform, data are analyzed and, following precise variant calling, mutations/alterations are detected. 4. Results/recommendations are clinically evaluated and presented (reporting). The analysis potentially detects all possible mutations, in 569 genes related to more than 300 severe or less severe genetic disease. PreDNA Test includes all genes to be tested during prenatal diagnosis, according to Obstetrics/Gynecology and Geneticist’s societies recommendations.

• Sensitivity is estimated to be approximately 99%.
• Only genes included in the detailed gene panel list are investigated and variant classification is based on database data entries and literature available at the particular time of analysis.
• The method is based on next generation sequencing and bioinformatics analyses of data derived from all exons of genes listed, their intron/exon boundaries as well as other known regulatory elements located outside genes and which are known to contribute to an abnormal phenotype. Intronic regions or other genes which might contribute/influence gene expression are not included in the analysis.
• Deletions, duplications or insertions larger than 20 bp, which are detectable by other methods, are not included in the analysis.
• Gonadal mosaicism (mutations confined in sperm/oocytes) is not detected since DNA analyzed is extracted from somatic cells.
• A negative result for the genes investigated may not exclude the occurrence of a de novo mutation in offspring.


PreDNA Test Gene Panel

The full list of genes tested with PreDNA Test

For further information please contact us