Extended Screening

Peace of Mind for Planned Pregnancies

Extended Carrier Screening is an important tool for prospective parents to help them determine their risk of having a child affected with a heritable disease. In many cases parents do not have any idea that they are carriers and have no family history or health symptoms due to the rarity of some diseases in the general population. Through Next Generation Sequencing (NGS) we are able to conduct Extended Carrier Screening (ECS), Extended Carrier Screening consists of a large panel that is able to analyse specific genes that are associated with hundreds of autosomal recessive and X-linked disorders to prospective parents in a general mixed population.^[1] Paternity For Life offers a comprehensive Extended Carrier Screening test, providing prospective parents with the information they require when planning their pregnancy, it has also been recommended that extended carrier screening is offered to all women when planning a pregnancy, regardless of their geographic origin or family history.^[2] Extended Carrier Screening has been shown to detect carriers who would not have been considered candidates for traditional risk-based screening.^[3] With a simple mouth swab collection, we are able to test for over 419 genes associated with inherited diseases, including Cystic Fibrosis, Spinal Muscular Atrophy and Fragile X Syndrome. If your gene of interest is not covered on our Extended Carrier Screening panel, please contact our friendly team to assist you in finding the gene test panel that suits your needs.

Why do genetic testing with Paternity For Life?

Approximately 1-2 of every 100 couples within the general population are at risk of being a carrier for an autosomal recessive genetic condition.^[5] Extended Carrier Screening for couples who are considering starting a family, aims to identify if each individual may be a carrier for the same autosomal recessive genetic condition. Extended Carrier Screening prior to pregnancy enables couples to learn about their reproductive risk and consider the most complete range of reproductive options, including whether or not to become pregnant, use of advanced reproductive technologies such as preimplantation genetic diagnosis or to use donor gametes. Screening also allows couples to consider prenatal diagnosis and pregnancy management options in the event of an affected fetus. At Paternity For Life we understand the sensitivities surrounding testing and we can assure you we strive to provide all of our patients with the highest level of professionalism, care and compassion. We offer an easy mouth swab collection kit that can be done in the comfort of your home and our laboratory handles your sample from start to finish.

What genetic conditions are tested by the Extended Carrier Screening?

Our Extended Carrier Screening enables detections of single nucleotide variants (SNVs), insertion/deletions (indels), and copy number variants (CNVs) over 419 genes associated with more than 700 unique commonly inherited diseases including the most common forms of inherited deafness, blindness, heart disease, immunodeficiency, and various ataxias, anaemias, and treatable metabolic syndromes. The assay has been developed to match genes targeted by clinical molecular geneticists studying inherited diseases, including genes listed in the NIH Genetic Test Registry. The clinical utility of this panel lies within the scope of pre-marital screening as well as pre-IVF screening. Please see below for a full list of genes covered on our Extended Carrier Screening panel and the associated genetic conditions.

My partner and I don’t have any diseases, how can we pass it on to our children?

An inherited disease is a disease or disorder caused by an abnormality in our DNA which affects cells throughout our body. The result of the abnormality can range from almost indistinguishable through to major problems. More than 6000 disorders are caused by changes in a single gene and are known as monogenic or Mendelian disorders, resulting in disease in about 1 in every 200 births.^[4]

What is an autosomal recessive condition?

Diseases are inherited in different ways, but many are inherited in what is called an “autosomal recessive” pattern, meaning that people that have one abnormal mutation will not have symptoms of the disease, rather being a “carrier” of that disease. If two carriers of an autosomal recessive disease have a child there is a 1/4 risk of the child being affected by that disease. To have an autosomal recessive condition, you inherit two affected genes, one from each parent. These conditions are usually passed on by two carriers (biological mother and father). The parents’ health is rarely affected, but they have one affected gene (recessive gene) and one unaffected gene (dominant gene) for the genetic condition. There is a 25% chance of two carriers having an unaffected child with two unaffected genes, a 50% chance of having a child who also is a carrier but is unaffected by the genetic condition, and a 25% chance of having an affected child who inherits the two recessive genes.^{[6, 7]}

What is an X-linked genetic condition?

X-linked genetic conditions, such as Fragile X Syndrome are caused by variants in genes located on the X chromosome. As males only have one X chromosome, they will be more affected by an X-linked condition in comparison to females, who have two X chromosomes. Females are more likely to be an asymptomatic carrier of an X-linked condition.^[6] Paternity For Life is able to screen for Fragile X Syndrome. It is an inherited X-linked genetic condition that is known to cause a range of developmental problems (such as cognitive impairment and learning disabilities).^{[8, 9]} It is estimated that only 1 in 4,000 males and 1 in 8,000 females are diagnosed with Fragile X syndrome, although it is a lot more common to be a carrier of the Fragile X Syndrome, with an estimated 1 in 150 females and 1 in 800 males being premutation carriers of the FMR1 gene.^[10] Fragile X Syndrome carriers are at risk of passing on the affected FMR1 gene to their children or grandchildren, resulting in Fragile X Syndrome.^[10]

We have a family history of a particular disease, should we be tested?

In cases where there is a known family history of a disease, carrier testing is an important tool for family planning and can guide reproductive options. In some cases, prospective parents will discover that they do not carry the familial mutation and therefore have a reduced risk for having a child with the disease.

If our results are negative does that mean our child will not be affected by a disease on this panel?

Genetic tests cannot detect all of the possible gene variants that could cause a disorder. This means that, even if you test negative, there is still a chance of having, or being a carrier of, one or more of the diseases associated with the genes which were tested. This is called Residual Risk. Please contact us for further information.

If my results show that both my partner and I are carriers, what can we do?

If prospective parents are both shown to be carriers of a genetic disorder, couples may choose to use assisted reproductive technologies such as IVF to become pregnant. Paternity For Life can then assist in screening embryos to reduce the risk of having an affected child. Paternity For Life recommends discussing all options with a genetic counsellor.

Ready to take control of your pregnancy?

Paternity For Life aims to educate patients and their families about inherited diseases and their risk of inheritance, to empower them with the knowledge to take control of their health and treatment plans. As each patient’s case is unique, there is no “one size fits all” when it comes to testing. As inherited disease testing and the results from such tests can be complex, we also recommend you seek Genetic Counselling both prior to and after testing to help you understand your results and the implications they may have for both you and your family. If you are ready to proceed with testing, a Testing Request Form can be downloaded from our website. We recommend you book an appointment with your doctor to discuss the testing and have your Request Form signed. You can then head to our website to submit your order and payment. Paternity For Life will then send a testing kit directly to your home address. All that is required for testing is a simple, painless mouth swab. Once we receive your sample we will begin testing. Results are typically available to your doctor within 21 working days.

How to Organise Testing?

1. Download our request form.
2. Book an appointment with your doctor or healthcare professional to discuss the testing and have the request form signed.
3. Head to our simple, easy-to-use order page to order your test.
4. Paternity For Life will send you a testing kit for collection of your sample.
5. Your personalised report is issued to your health care provider in 21 working days.

Technical Information

Testing targets specific gene mutations and does not detect mutations that are outside of the targeted area. Testing does not completely sequence every exon of each one of the genes. For Ion Torrent sequencing, the limit of detection is 5% at 500X coverage and 10% at 200X coverage. The limit of detection for sequencing is ~1%. For medical practitioners seeking further technical information regarding the assay, please contact Paternity For Life. For medical practitioners seeking further technical information regarding the assay, please contact Paternity For Life.

The Extended Carrier Screening Panel provides comprehensive coverage of common and rare variants to help achieve higher per-disorder detection rate. The panel targets >14,000 amplicons that cover all coding regions of 420 target genes, including intron/exon boundaries, to genotype more than 28,000 SNVs and indels from the ClinVar archive of human variation. The panel also provides robust targeting for CNV analysis to maximise carrier status detection. Genetic variants for a number of the most prevalent yet serious disorders can be difficult to resolve by NGS assays, and so separate additional stand-alone tests are often required. The Extended Carrier Screening Panel consolidates such stand-alone assays into a single assay, including difficult-to-sequence genes, such as SMN1 for spinal muscular atrophy, GBA for Gaucher disease, CYP21A2 for 21-hydroxylase deficient congenital adrenal hyperplasia, and HBA1 and HBA2 for alpha thalassemia.

References

1. Nijmeijer, S., Conijn, T., Lakeman, P., Henneman, L., Wijburg, F., & Haverman, L. (2019). Attitudes of the general population towards preconception expanded carrier screening for autosomal recessive disorders including inborn errors of metabolism. Molecular Genetics And Metabolism, 126(1), 14-22. doi: 10.1016/j.ymgme.2018.12.004
2. Genetic carrier screening. (2019). Retrieved 21 May 2021, from https://ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Genetic-carrier-screening(C-Obs-63)New-March-2019_1.pdf?ext=.pdf
3. Lazarin, G., Haque, I., Nazareth, S., Iori, K., Patterson, A., & Jacobson, J. et al. (2012). 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, 15(3), 178-186. doi: 10.1038/gim.2012.114
4. Sateesh, M. (2008). Bioethics and biosafety. New Delhi: I.K. International Publishing House.
5. Ropers, H. (2012). On the future of genetic risk assessment. Journal Of Community Genetics, 3(3), 229-236. doi: 10.1007/s12687-012-0092-2\
6. Autosomal recessive inheritance pattern. (2021). Retrieved 14 May 2021, from https://www.mayoclinic.org/autosomal-recessive-inheritance-pattern/img-20007457
7. Genetics, H., & Conditions, I. (2021). What are the different ways a genetic condition can be inherited?: MedlinePlus Genetics. Retrieved 14 May 2021, from https://medlineplus.gov/genetics/understanding/inheritance/inheritancepatterns/
8. Garber, K., Visootsak, J., & Warren, S. (2008). Fragile X syndrome. European Journal Of Human Genetics, 16(6), 666-672. doi: 10.1038/ejhg.2008.6
9. Fragile X syndrome: MedlinePlus Genetics. (2021). Retrieved 19 May 2021, from https://medlineplus.gov/genetics/condition/fragile-x-syndrome
10. Fragile X syndrome | Betterhealth.vic.gov.au. (2021). Retrieved 19 May 2021, from https://www.betterhealth.vic.gov.au/health/ConditionsAndTreatments/fragile-x-syndrome