Preimplantation genetic diagnosis in the prevention of the haemoglobin disorders

  • S. Kahraman | Istanbul Memorial Hospital ART and Reproductive Genetics Center, Istanbul, Turkey.
  • G.C. Ekmekçi Istanbul Memorial Hospital ART and Reproductive Genetics Center, Istanbul, Turkey.
  • Ç. Beyazyürek Istanbul Memorial Hospital ART and Reproductive Genetics Center, Istanbul, Turkey.


Preimplantation Genetic Diagnosis (PGD) is currently an alternative for couples with high risk of pregnancies with genetic anomalies; it offers the possibility of avoiding the need to terminate affected pregnancies, since it allows the selection of unaffected embryos for transfer. PGD for inherited disorders has become extremely accurate (99.5%), and may currently be performed for any single gene disorders in which mutation is identified. PGD has been performed for more than 100 different conditions resulting in the birth of at least 1000 healthy children free of genetic disorder. PGD is presently also used together with preimplantation HLA typing for treatment of affected sibling with genetic and acquired disorders requiring HLA matched stem cell transplantation. This is not only to allow couples to have an unaffected child but also to select a potential donor progeny for stem cell transplantation. In Turkey, thalassemia is the most commonly seen genetic disorder the rate of thalassemia carriers is about 3 - 4% in Turkey. The majority of our PGD cases are thalassemia carriers. They do not only require thalassemia mutation analysis but also HLA typing for their affected child. In this study PGD results of 236 Turkish couples with or without HLA typing will be presented and discussed. A full diagnosis was achieved in 91.0% of the biopsied samples. In Group I, 17.8% of the analyzed embryos were found to be HLA compatible. HLA compatible and disease free embryos were 12.9% of all diagnosed embryos. In group II, 17.2% of embryos were found to be HLA matched and 71.4% HLA non-matched. The majority of our HLA typing combined with PGD cases were β-Thalassemia carriers (87.9%). The mutations analyzed have high heterogeneity, the most frequent mutation was IVS-I-110 G-A and comprised 46.2% of all mutations. To date, 70 healthy and HLA compatible children have been born. Twenty-five sick children have already been cured with cord blood cell and/or bone marrow transplantation. Twenty-one children are waiting for their newborn siblings to gain sufficient weight and maturity for the donation of stem cells. The successful transplantations have been performed for the following indications: β- Thalassemia (n=19), Wiskott Aldrich syndrome (n=2), Glanzmann Disease (n=1), X-Adrenoleukodystrophy (n=1) and acute myeloid leukemia (n=1) and Diamond Blackfan anemia (n=1). This data presents one of the world’s largest experiences on preimplantation HLA typing, and the outcome of stem cell transplantation is the largest number available from one center. Our results indicate HLA typing with or without mutation analysis is a promising and effective therapeutic tool for curation of an affected sibling.


如今,对于胎儿先天畸形的高风险夫妇来讲,可以选择植入前遗传学诊断(PGD),由于它能对未受地贫遗传的胎儿进行选择,因而能更有效地终止被遗传地贫的胎儿的出现几率。 遗传病植入前遗传学诊断(PGD)已日趋准确(准确率高达99.5%),如今,此方法也能用来诊断所有的确诊变异的单基因病。 植入前遗传学诊断(PGD)使至少一千多名本来可能患上遗传地贫的孩子免遭此劫难, 这些孩子中,情况不一,一百多种情况不尽相同,他们如今非常健康。现在,植入前遗传学诊断(PGD)还和胚胎植入前白细胞抗原配型一起使用,来治疗受感染的同胞种基因,以及HLA匹配的干细胞移植。 这不仅使夫妇能得到健康的孩子,还能为干细胞移植选择一个潜在的捐赠者后代。 在土耳其,地中海贫血是最常见的基因遗传病,土耳其的地贫基因携带者约为3%-4%。 我们的植入前遗传学诊断(PGD)的患者中大多数人都是地中海贫血基因携带者。 他们不仅仅被要求做地中海贫血基因突变分析,还给他们受到地贫基因遗传的孩子做HLA配型。 这份对植入前遗传学诊断(PGD)的研究结果对使用或没使用HLA配型的夫妇进行了展示和讨论。 在活体样本中,诊断的完整度达到了91.0%。 在第一组样本中,经过分析的胚胎中有17.8%与HLA匹配。 在全部诊断的胚胎中,HLA兼容和无遗传病基因的胚胎占12.9%。 在第二组样本中,有17.2%的胚胎与HLA匹配,71.4%不匹配。 我们的HLA配型与植入前遗传学诊断(PGD)中大多数案例都是β型地中海贫血基因携带者(占87.9%)。 经分析表明基因突变有高异质性,而最频繁的基因突变是IVS-I-110 G-A ,占总数46.2%。 迄今为止,70名健康的以及HLA配型成功的孩子已经降生。 25名患病儿童已在脐带血肝细胞以及/或者骨髓移植的治疗方法下得到康复。 21名患病儿童正在等待他们的同胞弟妹的出生以及成长,等他们体重达到捐献所规定的体重,以及成长到规定的年龄,就能获得他们捐出的干细胞。 移植手术已成功地在如下疾病中实施: β型地中海贫血(n=19)、德里症候群(n=2)、血小板无力症(n=1)、X-肾上腺白质营养不良症(n=1)、急性骨髓性白血病(n=1))、先天性纯红血球再生障碍性贫血(n=1)。 这份数据展示了关于胚胎植入前HLA配型世界上最丰富的经验之一,干细胞移植的成果已达到了一个中心所能成功的最大化。 我们的研究结果表明有或者无基因突变分析的HLA配型对于治疗有遗传病的胚胎,是前景广阔并且行之有效的一种治疗手段。



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hemoglobin disorders, genetic diagnosis.
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How to Cite
Kahraman, S., Ekmekçi, G., & Beyazyürek Ç. (2011). Preimplantation genetic diagnosis in the prevention of the haemoglobin disorders. Thalassemia Reports, 1(1), e5.