PGD to select HLA matched embryo for stem cell therapy for beta thalassemia

Background: Preimplantation genetic diagnosis (PGD) combines IVF with genetic testing, and it allows families to assure their child’s health regarding genetic disorders before pregnancy.Methods: A family with a 6 year old child were affected with beta thalassemia major and referred for PGD to have a non-thalassemic HLA-matched child whose stem cells can be used for transplantation for their affected child. This study was approved by Kawsar human genetics research center ethic committee. Mutation detection in the affected child and linked STR haplotypes were carried out. Fertilization was carried out at the IVF clinic. On day 3 post fertilization, one blastomere was removed from each of the 8 embryos and used for PGD. Mutations and informative STR markers (16 for HLA and 4 for HBB) were investigated for each cell using multiplex nested PCR. Fragment analysis of the PCR products were run on capillary electrophoresis and analyzed using GeneMapper® software. Unaffected HLA-matched embryos were selected and were implanted. Prenatal diagnosis (PND) was performed at 16th week of gestational age to verify PGD results.Result: HBB:c.51delC mutation was diagnosed in patients and from 8 analyzed blastomeres 2 (25%) were unaffected HLA-matched. The others were either affected or not-matched. Both embryos were implanted and PND confirmed PGD result. A singleton baby was born on 2015.02.14.Conclusion: PGD for a disease in combination with HLA typing was used to select HLA-matched embryo to have a potential donor for stem cell transplantation. İn case of successful IVF, using PND can minimize risks of misdiagnosis.

Keywords:

HLA typig , IVF , PND , Thalassemia , PGD