Pre-implantation genetic diagnosis (PGD) is an advanced genetic test that is used to screen embryos for a known mutation causing a familial genetic condition. A large proportion of families with a family history of a heritable genetic condition, such as β-Thalassaemia or sickle cell disease, already have a child who is affected by the condition. The use of stem cell transplants are potentially curable and rely on an HLA matched donor. PGD can be done in conjunction with HLA typing offering families a tool to conceive a child who is unaffected by a genetic condition and who is HLA matched to an affected sibling. At delivery, haematopoietic stem cells from the new-born’s umbilical cord blood is collected, which can be subsequently used to treat the affected sibling.
PGD is performed in conjunction with in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI). These techniques of assisted reproductive technology generate embryos outside of the body in the fertility clinic, which in turn allows access to the genetic material of the embryo. By removing a single or a few cells from each embryo, PGD is able to determine the disease status of each embryo. The purpose of PGD is therefore to identify genetically unaffected embryos prior to embryo transfer, which will hopefully give rise to a successful pregnancy and child that is free of the genetic condition. With the help of PGD, families affected by many inherited conditions can help reduce the risk of passing it on to their children.
β-Thalassaemia is one of the most common inherited blood disorders. Severely affected individuals require life-long blood transfusions, but frequent transfusions can cause iron overload and thus requires iron chelation treatment. The use of haematopoietic stem cell transplantation to treat conditions, such as β-Thalassaemia, has been increasing, with substantially increasing positive outcomes. Current experience world-wide is that more than 90% of patients now survive haematopoietic stem cell transplantation and disease-free survival is around 80%.
Bone marrow is one source of haematopoietic stems cells. Bone marrow transplants to individuals affected with β-Thalassaemia can be curative, eliminating the requirement for transfusions. However, transplants rely on the availability of an HLA matched donor. The chances of finding a matched donor is 1 in 100,000, which is important to consider in conjunction with the number of registered donors. These statistics can be even lower for families of ethnic minorities or mixed race couples as these HLA types are under-represented on bone marrow registries worldwide.
Umbilical cord blood is another source of hematopoietic stem cells. In 2003, the feasibility of using HLA-identical sibling cord blood for haematopoietic stem cell transplantation in β-Thalassaemia was first reported², and has subsequently been used to successfully transplant bone marrow to over 500 patients. However, a child has a 1 in 4 chance of being an HLA-match to an affected sibling. Based on this likelihood of finding an HLA-matched sibling is higher in large families (60-70%) ³, it is intuitively less likely in smaller families. Thus, for families with only a single child who is affected with β-Thalassaemia, the chances of having a second child that is free of the condition and an HLA match is 6.25%. PGD with HLA typing certainly increases these chances and these decisions should always be undertaken with thorough consultation with genetic counsellors, the paediatric haematology/oncology team as well as the fertility team.
Genesis Genetics is a leading global provider of pre-implantation genetic diagnosis and Screening (PGD/PGS) – providing expert laboratory services for many of the most respected in vitro fertilisation (IVF) centres across the country and throughout the world.
Genesis Genetics was founded by world-renowned scientists who are largely responsible for pioneering pre-implantation genetic diagnosis as a clinical practice. For more information on PGD, please contact:
Dr Jaysen Knezovich | Managing Director | firstname.lastname@example.org | 011697 2926
2. Locatelli F et al. Related Umbilical Cord Blood Transplantation in Patients with Thalassemia and Sickle Cell Disease. Blood. 2003; 101(6):2137–43.
3. Jawdat DM et al. Chances of Finding an HLA-matched Sibling: The Saudi experience. Biol Blood Marrow Transplant. 2009; 15(10):1342–4.