Application of NGS-based SNP haplotyping for preimplantation genetic diagnosis for beta-thalassemia and HLA matching / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To assess the value of next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping for preimplantation genetic diagnosis (PGD) for beta-thalassemia coupled with human leukocyte antigen (HLA) matching.@*METHODS@#Three couples were recruited. Couple 1 both carried a β (IVS-2-654) variation and had previously given birth to a son with β thalassemia major. Couple 2 respectively carried (cd41-42) and β (IVS-2-654) but had no history of pregnancy. Couple 3 respectively carried β (CD17) and β (IVS-2-654), and had a daughter carrying β (CD17).@*RESULTS@#For couple 1, NGS-SNP typing identified two embryos not only unaffected with thalassemia but also with matched HLA. One blastocyst was transferred and resulted in successful pregnancy. A healthy baby was born at 39th week of gestation. Its umbilical blood was used to treat the sick brother through hemopoietic stem cell transplantation. For couple 2, seven blastocysts were obtained. Second transplantation has resulted in successful pregnancy. Prenatal diagnosis was consistent with PGD. For couple 3, two blastocysts not only unaffected with thalassemia but also with no pathogenic copy number variations were obtained. Transfer of one blastocyte resulted in successful pregnancy, and prenatal diagnosis was consistent with PGD.@*CONCLUSION@#NGS-based SNP typing is an useful tool for selecting embryos unaffected with beta-thalassemia and matched HLA through PGD.