Thalassemia HBB

The list of mutations for which we performed PGD was presented in Chapter 3. Thalassemias are among the most common single-gene disorders, requiring lifelong blood transfusion and iron chelation therapy, with the only radical treatment being HLA-compatible bone marrow transplantation, as describe in Chapters 3 and 4. As shown in those chapters, thalassemia is one of the major indications of PGD combined with preimplanta-tion HLA typing, so this provided the possibility of the establishment of ES cell lines, one of which is shown in Figure 7.5.

As seen from the pedigree, the parents were carriers of different mutations, the father carrying Cd39 and the mother IVS I-110 mutation, both being the most common mutations in the Mediterranean region. They had one previous child affected with severe beta-thalassemia, requiring HLA-compatible bone marrow transplantation. So the couple requested PGD and HLA typing, which was performed by blastomere biopsy and multiplex PCR analysis, involving simultaneous testing of both mutation and HLA markers, described previously in Chapter 4. Of 10 embryos tested, three were affected (embryos #1, 6, and 7), one contained only one chromsome 11 with Cd 39 mutation, while the remaining six were carriers of one of the mutations. Only one of these embryos was a full HLA match and transferred. Of the six affected embryos four were donated for research, including embryo #1, which was also an HLA nonmatch, resulting in the establishment of ES cell line hESC-164. The follow-up testing showed that the cells are compound heterozygous affected for Cd39 and IVSI-110 mutations.

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