Genescreen
Genescreen is a screening test that allows for the identification of healthy carriers of multiple genetic diseases in order to assess the patient's reproductive risk in relation to hereditary monogenic disorders.
Genescreen offers a broad-spectrum analysis that enables patients to make more informed reproductive decisions: undergoing Genescreen before pregnancy allows future parents to gain greater awareness of their reproductive health.
Various international scientific organizations have published guidelines for the use of carrier screening, including its benefits, limitations, and technical and ethical considerations (ACOG, ACMG, RANZCOG, SIGU).
GENESCREEN
Available panels
GENESCREEN
Who it's recommended for
Genescreen can be used as a family planning tool, allowing future parents to take the test individually or with their reproductive partner to assess the risk of having children affected by genetic disorders.
It has been shown that most people are carriers of at least one genetic disease and are usually unaware of their carrier status because they are healthy and have no family history indicative of specific genetic disorders.
For this reason, screening can be offered before or during pregnancy to all women of reproductive age and their reproductive partners, as well as to gamete donors (egg or sperm donors).
Genescreen is particularly recommended in certain circumstances, especially when there is consanguinity (established or suspected), when both partners come from a small region, or when they belong to a specific genetic ancestry (e.g., Ashkenazi Jews, Finns).
Having a positive family history of a genetic disease is an indication for preconceptional/prenatal carrier screening; however, it is advisable to discuss the best testing options with a healthcare specialist or a genetic counselor.
GENESCREEN
Analysis method
Genescreen combines various genetic analysis methodologies and bioinformatics pipelines to provide comprehensive carrier screening that detects pathogenic variants in hundreds of genes.
The analysis performed using Next Generation Sequencing (NGS) is designed to examine the coding regions and splice junctions of the genes included in the test.
The sequencing analysis allows for the detection of single nucleotide variants (SNVs) and large deletions/duplications in the analyzed genes.
The variants are classified according to ACMG/AMP interpretation standards using public databases, including dbSNP-NCBI, ClinVar-NCBI, and gnomAD. Only pathogenic or likely pathogenic variants will be reported.
Benign variants, likely benign variants, and variants of uncertain significance will not be reported, but they may be noted under certain circumstances. The classification of variants is based on the understanding of the genes and variants at the time of analysis; further knowledge acquired in the future may lead to the reclassification of the identified variants.
Although NGS technology and bioinformatics analysis significantly reduce the impact of pseudogene sequences or other highly homologous sequences, these can still occasionally interfere with the technical ability of the analysis to identify pathogenic variants.
Orthogonal methods may be used to confirm variants with low quality scores and to meet coverage standards.
This test will not detect certain types of genomic alterations that can cause diseases, including translocations and inversions, repeat expansions (e.g., trinucleotide or hexanucleotide repeats), alterations in most regulatory regions (e.g., promoter regions), or intronic regions more than 20 bp from an exon.
This test is not designed or validated to detect somatic mosaicism events or somatic mutations.
The carrier test for Fragile X provides information on the carrier status of Fragile X Syndrome, which is caused, in the majority of cases, by expansions in a repeated sequence (CGG)n.
The test is performed using fluorescent PCR amplification of the trinucleotide repeat region located in the 5' UTR of the FMR1 gene.
The method does not allow for the detection of single nucleotide variants (also known as point mutations), gene deletions and/or duplications, or the methylation status of the gene.
The analytical detection rate of Genescreen is high and varies depending on the individual diseases. The residual risk is the probability that the tested patient is a carrier even after testing negative on the screening test.
The residual risk is closely related to the frequency of carriers of the disease and the detection rate of the test for that condition.
The frequency of carriers can vary widely among different populations/ethnic groups. The residual risk provided by Genescreen is calculated using an internal algorithm.
Scientific publications in support
- Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129e35-40.
- Carrier screening for genetic conditions. Committee Opinion No. 691. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129: e41-55.
- Edwards et al. Expanded Carrier Screening in Reproductive Medicine--Points to Consider. A Joint Statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol 2015; 1253.
- Genetic carrier screening. Royal Australian and New Zealand College of Obstetricians and Gynaecologists, RANZCOG. 2022. https://ranzcog.edu.au/wp-content/uploads/2022/05/Geneticcarrier-screeningCObs-63New-March-2019_1.pdf.
- Cavalli P, Capalbo A, Novelli V, Zuccarello D, Lonardo F, Giardina E, Calabrese O, Bizzoco D, Bianca S, Scarano G, Grati FR. Considerazioni sull'utilizzo del Carrier Screening (CS) ed Expanded Carrier Screening (ECS) in ambito riproduttivo. Italian Society of Human Genetics, SIGU. 2021. https://sigu.net/wp-content/uploads/2021/10/ConsiderazionisullutilizzodelCarrierScreeningCSedExpandedCarrierScreeningECSinambitoriproduttivorev20_07_2021.pdf.
- Miller DT, Lee K, Abul-Husn NS, Amendola LM, Brothers K, Chung WK, Gollob MH, Gordon AS, Harrison SM, Hershberger RE, Klein TE, Richards CS, Stewart DR, Martin CL; ACMG Secondary Findings Working Group. Electronic address: documents@acmg.net. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023 Aug;25(8):100866.