Preimplantation Genetic Diagnosis for Hemoglobinopathies

Abstract

Hemoglobinopathies are the most frequent indications for preimplantation genetic diagnosis (PGD), allowing couples at-risk of bearing offspring with thalassemia and sickle cell disease to reproduce without fear of having an affected child. The present experience includes PGD for sickle cell disease, α- and β-thalassemia (α- and β-thal). We present here the results of the world's largest experience of over 395 PGD cycles for hemoglobin (Hb) disorders, resulting in the birth of 98 healthy, hemoglobinopathy-free children, with seven pregnancies still ongoing. One-third of these cases were performed in combination with HLA typing, allowing the birth of unaffected children who were also HLA identical to the affected siblings with hemoglobinopathies in these families, with successful or pending stem cell transplantation in a dozen of them. The results show that PGD is presently a practical approach for prevention of hemoglobinopathies, gradually also becoming a useful approach to improving access to HLA-compatible stem cell transplantation for this group of diseases.

The Prevention of Thalassemia

“…Diagnosis was obtained by multiple nested PCR analysis to detect the mutations as well as polymorphic alleles at the b-globin cluster (Kuliev et al 2011;Zachaki et al 2011). HLA typing of the embryo to select a nonaffected fetus HLA compatible with a previous affected sibling was recently proposed (Kuliev et al 2011).…”

“…This approach minimizes the risk of misdiagnosis that could result from PCR failure, contamination, and allelic dropout that is a definite risk in single-cell analysis. In a large series, misdiagnosis was rare and the pregnancy rate high (32%) (Kuliev et al 2011). The motivations for couples following counseling to opt for preimplantation genetic diagnosis (PGD) are problems of infertility, an unsuccessful reproductive history owing to repeated terminations of affected fetuses, moral or religious attitude against pregnancy termination, and the desire to have a nonaffected fetus HLA compatible with a previously homozygously affected sibling for future bone marrow transplantation.…”

Prevention of sickle cell disease: observations on females with the sickle cell trait from the Manchester project, Jamaica

“…Fetal diagnosis is now simpler and more accurate but with the social and cultural concerns regarding termination of affected pregnancies, the family desires information on the likely clinical course which is currently almost impossible to predict. Preimplantation genetic diagnosis (Xu et al 1999) requires facilities for in vitro fertilisation which are limited in high-risk areas, are expensive and have success rates of 40-50 %, although its acceptability for sickle cell disease is expanding in the USA (Kuliev et al 2011). However, these technologies are not widely available in developing societies and neither prenatal diagnosis nor pre-implantation genetic diagnosis is currently offered in Jamaica.…”

Preimplantation HLA Typing for Stem Cell Transplantation Treatment of Hemoglobinopathies

“…[6][7][8][9] We have previously reported the results of PGD for thalassemia, with simultaneous HLA typing, resulting in birth of thalassemia-free HLA matched children, as donors of cord blood and/or bone marrow for transplantation treatment for their affected siblings. 10,11 The present paper describes the progress in PGD for hemoglobinopathies with preimplantation HLA typing, demonstrating that PGD has become an acceptable approach for HLA matched stem cell transplantation treatment for hemoglobinopathies.…”