Adventia carrier screening

Adventia is suitable for individuals or couples seeking reproductive genetic screening, including:

• Couples planning to start their families and wanting to know about their carrier status
• Any individual or couple going through assisted reproduction, including in vitro fertilisation (IVF)
• Sperm and oocyte donors, and recipients of sperm or oocyte donation
• Couples who are already pregnant and want to know whether their child has a risk of having a genetic disorder
• High-risk population groups for specific disorders
• People with a family history of a genetic mutation
• Any individual wishing to know more about their genetic profile

1 in 4 people is a carrier of a genetic disorder. Genetic disorders may be rare, with varying prevalence, but can have adverse effects on health and development, or even be life-threatening. Without carrier screening, asymptomatic carriers of recessive mutations often discover their carrier status only after they have an affected child.

Early knowledge of one’s carrier status and of their subsequent risk of transmitting a genetic disorder to their children can:

• Help individuals evaluate their reproductive options to prevent that risk
• Result in earlier interventions and therapies where available
• Lead to better clinical management of affected children

Recommendations and statements from international organisations:

• Carrier screening information should be provided to all pregnant women
• Published evidence supports clinical utility for carrier screening of multiple conditions simultaneously
• Carrier screening panels should be neutral to ethnicity and population, and more inclusive of diverse populations in order to promote equality and inclusion

Clinically significant variant detected

A pathogenic or likely pathogenic variant has been identified in a gene tested. The patient is a carrier of the associated disorder. Sometimes, two disease-causing variants in the same gene may be found. In this case, the patient is either affected now or may be affected in the future by the associated disorder. Variant classification based on / criteria.

No clinically significant variant detected

No disease-causing genetic variant has been identified in the genes tested.

Variants of unknown significance (VUS) are not reported as per joint statement of , , , and .

Depending on the results, there are multiple choices you can recommend to your patients:

• Genetic counselling, if applicable
• Prenatal diagnosis during pregnancy
• IVF and preimplantation genetic testing for monogenic disorders (PGT-M)
• Choice of compatible gamete donor without the same mutation
• Early intervention, therapies where

Genetic counselling is a specialised, patient-centred, impartial, and non-directive communication process that supports patients and their families both before and after genetic testing.

Prior to genetic testing, genetic counsellors obtain a detailed medical and family history and provide education on genetic concepts, the testing process, and available options, along with the potential risks, benefits, limitations, and possible outcomes.

Upon receiving genetic test results, genetic counsellors assist in interpreting the findings and guide individuals through the implications for their own personal health and that of their family members. During post-test counselling, genetic counsellors also provide evidence-based recommendations on next steps, including strategies for prevention, surveillance, and management.

The goal of genetic counselling is to empower patients through knowledge and tailored support, enabling them to make informed and voluntary decisions

Adventia uses targeted next-generation sequencing (NGS) combined with validated bioinformatic analysis to identify clinically relevant genetic variants associated with inherited disorders. The assay has been extensively validated to provide accurate, reliable and reproducible carrier screening across the genes included in each panel.

Adventia analyses the coding regions of the selected genes*, together with clinically relevant adjacent non-coding regions, to maximise the detection of disease-causing variants. The assay is designed to detect multiple clinically relevant variant types, including:

• Single nucleotide variants (SNVs)
• Small insertions and deletions (INDELs)
• Copy number variants (CNVs)

Sequencing data are analysed using validated bioinformatic pipelines that support the accurate identification and classification of clinically relevant variants, contributing to the analytical performance of the assay. By combining targeted sequencing with comprehensive variant detection and advanced bioinformatic analysis, Adventia provides high-quality genetic information to support reproductive risk assessment and informed clinical decision-making.

Variant classification based on / criteria.

*Coverage exceptions apply to certain disorders and genomic regions that present recognised technical limitations, including repetitive sequences, regions of high homology (such as pseudogenes and segmental duplications), or regions with extreme GC content.

The following information applies to Adventia Focus panels:

• A-Thalassemia: Analysis performed via MLPA
• B-Haemoglobinopathies: Analysis performed via Sanger Sequencing
• Cystic fibrosis: Analysis performed via Next Generation Sequencing
• Duchenne muscular dystrophy: Analysis performed via MLPA
• Fragile X syndrome: Analysis performed via Fragmentation analysis
• Spinal muscular atrophy: Analysis performed via MLPA

Testing for A-Thalassemia, B-Haemoglobinopathies and Dystrophinopathies via the Core and Comprehensive panels yields higher detection rates

• Lazarin GA, Haque IS, Nazareth S, Iori K, Patterson AS, Jacobson JL, et al. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Genetics in Medicine. 2012 Sep 13;15(3):178–86. doi: 10.1038/gim.2012.114. PMID: . PMCID: PMC3908551.
• American College of Obstetricians and Gynecologists. Committee Opinion No. 691. Obstetrics & Gynecology. 2017 Mar;129(3):e41–55. doi:10.1097/aog.0000000000001952. PMID: .
• Edwards JG, Feldman G, Goldberg J, Gregg AR, Norton ME, Rose NC, et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider. Obstetrics & Gynecology. 2015 Mar;125(3):653–62. doi:10.1097/aog.0000000000000666. PMID: .
• Gregg AR, Aarabi M, Klugman S, Leach NT, Bashford MT, Goldwaser T, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine. 2021 Oct;23(10):1793–806.  doi:10.1038/s41436-021-01203-z. PMID: . PMCID: PMC8488021.