Cao A, Rosatelli C, Pirastu M
J Genet Hum. 1986 Nov;34(5):413-24.
In this paper we reviewed the different methods presently available for prenatal diagnosis of hemoglobin disorders and the impact of this technology in the control of beta-thalassemia in several Mediterranean populations. The vast majority of the inherited hemoglobinopathies can now be detected in the fetus by amniocyte or trophoblast DNA analysis. alpha-thalassemias, delta beta-thalassemias and gamma delta beta-thalassemias, which are usually caused by a gross structural rearrangement of the DNA, may be directly detected by Southern blot analysis. Only a few beta-thalassemia lesions are caused by gene deletion or affect a restriction recognition site and thus may be directly identified by this method. The major part of beta-thalassemia are due to single nucleotide substitution, small deletion or addition which do not alter a restriction recognition site. These mutations may be directly detected by complementary oligonucleotide probes. Alternatively, when normal or affected children are available, fetal diagnosis may be accomplished by linkage analysis with polymorphic restriction sites. Fetal blood analysis is used at present time for those cases presenting too late in the pregnancy for characterization of the molecular defect and in prospective parents in whom the defect is not known. Introduction of prenatal diagnosis in combination with carrier screening in several mediterranean populations led to a consistent reduction in the incidence of homozygous beta-thalassemia.
在本文中，我们回顾了目前可用于血红蛋白疾病产前诊断的不同方法，以及该技术对几个地中海人群中β地中海贫血控制的影响。现在，通过羊水细胞或滋养层细胞DNA分析，绝大多数遗传性血红蛋白病都能在胎儿中被检测出来。α地中海贫血、δβ地中海贫血和γδβ地中海贫血通常由DNA的大规模结构重排引起，可通过Southern印迹分析直接检测。只有少数β地中海贫血病变是由基因缺失引起的，或影响一个限制性识别位点，因此可通过该方法直接识别。β地中海贫血的主要部分是由于单核苷酸取代、小的缺失或插入，这些不会改变限制性识别位点。这些突变可通过互补寡核苷酸探针直接检测。另外，当有正常或患病儿童时，胎儿诊断可通过与多态性限制性位点的连锁分析来完成。目前，胎儿血液分析用于那些怀孕后期才出现、无法确定分子缺陷特征的病例，以及父母中缺陷未知的准父母。在几个地中海人群中引入产前诊断并结合携带者筛查，使得纯合子β地中海贫血的发病率持续下降。
