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Preimplantation genetic diagnosis (PGD) has recently been offered in combination with HLA typing, which allowed a successful haematopoietic reconstitution in affected siblings with Fanconi anaemia by transplantation of stem cells obtained from the HLA-matched offspring resulting from PGD. This study presents the results of the first PGD practical experience performed in a group of couples at risk for producing children with genetic disorders. These parents also requested preimplantation HLA typing for treating the affected children in the family, who required HLA-matched stem cell transplantation. Using a standard IVF procedure, oocytes or embryos were tested for causative gene mutations simultaneously with HLA alleles, selecting and transferring only those unaffected embryos, which were HLA matched to the affected siblings. The procedure was performed for patients with children affected by Fanconi anaemia (FANC) A and C, different thalassaemia mutations, Wiscott–Aldrich syndrome, X-linked adrenoleukodystrophy, X-linked hyper-immunoglobulin M syndrome and X-linked hypohidrotic ectodermal displasia with immune deficiency. Overall, 46 PGD cycles were performed for 26 couples, resulting in selection and transfer of 50 unaffected HLA-matched embryos in 33 cycles, yielding six HLA-matched clinical pregnancies and the birth of five unaffected HLA-matched children. Despite the controversy of PGD use for HLA typing, the data demonstrate the usefulness of this approach for at-risk couples, not only to avoid the birth of affected children with an inherited disease, but also for having unaffected children who may also be potential HLA-matched donors of stem cells for treatment of affected siblings.
- Ethical implications of a new application of preimplantation diagnosis.Journal of the American Medical Association. 2001; 285: 3143-3144
- Social and ethical issues of PGD, cloning and gene therapy.Reproductive BioMedicine Online. 2003; 6: 170-180
- Microsatellite in the HLA region: 1999 update.Tissue Antigens. 2000; 55: 477-509
- Conception for donation.Journal of the American Medical Association. 2004; 291: 2125-2126
- Thirteen years' experience of preimplantation diagnosis: report of the Fifth International Symposium on Preimplantation Genetics.Reproductive BioMedicine Online. 2004; 8: 229-235
- Birth of healthy children after reimplantation diagnosis of thalassemias.Journal of Assisted Reproduction and Genetics. 1999; 16: 207-211
Online Mendelian Inheritance in Man (OMIM) 2001 Johns Hopkins University http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM [accessed 21 June 2004].
- Somatic cell haploidization: an update.Reproductive BioMedicine Online. 2003; 6: 60-65
- Novel universal approach for preimplantation genetic diagnosis of β-thalassemia in combination with HLA matching of embryos.Human Reproduction. 2004; 19: 700-708
- Atlas of Preimplantation Genetic Diagnosis. Parthenon, New York, London2000
- Preimplantation diagnosis for Fanconi anemia combined with HLA matching.Journal of the American Medical Association. 2001; 285: 3130-3133
- Preimplantation HLA typing.Journal of the American Medical Association. 2004; 291: 2079-2085
Dr Svetlana Rechitsky is a graduate of Kharkov University's Genetics Faculty, and received her PhD in Experimental Molecular Embryology from the Second Moscow Medical Institute in 1986. She moved to the Reproductive Genetics Institute in 1989 to head the DNA laboratory, which has performed the largest preimplantation genetic diagnosis (PGD) series for single gene disorders, with PGD design for the majority of these disorders developed for the first time. She has published more than 30 papers in the field of PGD, including a key contribution to the recently published Atlas of Preimplantation Genetic Diagnosis.
Accepted: June 16, 2004
Received: May 21, 2004
© 2004 Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB23 8DB, UK. Published by Elsevier Inc. All rights reserved.