Prenatal diagnosis of thalassaemia.
Prenatal diagnosis of thalassaemia.
复制标题
地中海贫血的产前诊断。
作者：
D. Weatherall
世界卫生组织最近的一份报告表明，世界上有超过2亿的遗传性血红蛋白疾病携带者，每年有20万至30万名严重受累的纯合子或复合杂合子出生。对这些疾病进行对症治疗既昂贵又不令人满意，因此预防这些疾病是许多国家的主要公共卫生目标。对镰状细胞性贫血临床病程的不确定性限制了人们开发大规模宫内检测项目的热情。另一方面，几乎没有人怀疑为地中海贫血症家庭设立遗传咨询和产前诊断服务的价值。事实上，由于携带者很容易识别，而且对分子变化有如此多的了解，地中海贫血症已经成为将新的直接基因分析形式应用于单基因疾病产前诊断的模式。地中海贫血症的产前诊断有几种方法。2虽然这项技术具有直接测量突变珠蛋白基因产物的优点，但要到怀孕18周左右才能使用，这意味着母亲要等待很长一段时间，如果需要的话，终止妊娠也相对困难。最近开发的直接基因分析技术3可以通过从羊水细胞中分离的胎儿脱氧核糖核酸(DNA)诊断某些形式的地中海贫血症。4 6然而，在不首先在培养物中培养数周的情况下，并不总是能够获得足够的细胞来制造DNA，所以这再次意味着诊断较晚。相比之下，新开发的从妊娠前三个月的滋养层绒毛活检标本中获取胎儿DNA的方法7使地中海贫血症和镰状细胞性贫血的产前诊断得以更早。9没有积累足够的经验来了解滋养层活检是否导致不可接受的胎儿缺失率，或者它是否对儿童有任何有害的长期影响。这些问题的答案可能需要几年时间。如果我们要从久经考验的胎儿血液采样方法转向用于地中海贫血症产前诊断的胎儿DNA分析，则需要清楚地了解潜在的科学基础。过去几年的研究表明，地中海贫血症是由许多不同的突变引起的。在某些情况下，主要基因缺失或重排，但在大多数情况下，分子损伤更多。
A recent report from the World Health Organisation suggests that there are over 200 million carriers for inherited disorders of haemoglobin in the world and that between 200 000 and 300 000 severely affected homozygotes or compound heterozygotes are born each year.1 The most important of these conditions are a and 3 thalassaemia and sickle cell anaemia. Symptomatic treatment of these disorders is expensive and unsatisfactory, so their prevention is a major public health goal in many countries. Uncertainty about the clinical course of sickle cell anaemia has limited enthusiasm for developing large scale programmes for its detection in utero. On the other hand, few doubt the value of setting up genetic counselling and prenatal diagnosis services for families with thalassaemia. Indeed, because carriers are easily identified and so much is known about the molecular changes thalassaemia has become the model for applying the new forms of direct gene analysis to prenatal diagnosis of single gene disorders. The prenatal diagnosis of thalassaemias may be approached in several ways. Fetal blood sampling and measurement of globin chain synthesis by radiolabelling have been used successfully in many countries.2 Though this technique has the advantage of directly measuring the products ofthe mutant globin genes, it cannot be used until about the 18th week of pregnancy-which means a long wait for the mother, and, if indicated, a comparatively difficult termination of pregnancy. The recently developed techniques of direct gene analysis3 allow the diagnosis of some forms of thalassaemia from fetal deoxyribonucleic acid (DNA) isolated from amniotic fluid cells.4 6 It is not always possible, however, to obtain enough cells to make DNA without first growing them in culture for several weeks, so again this implies a late diagnosis. By contrast, the newly developed methods for obtaining fetal DNA from biopsy specimens of trophoblastic villi in the first trimester of pregnancy7 have allowed the prenatal diagnosis of thalassaemia and sickle cell anaemia much earlier.8 9 Insufficient experience has been accumulated to know whether trophoblastic biopsy causes an unacceptable rate of fetal loss or whether it has any deleterious long term effects on the child. Answers to these questions may take several years. If we are going to move from the well tried method of fetal blood sampling to fetal DNA analysis for the prenatal diagnosis of the thalassaemias the underlying scientific basis needs to be clearly understood. Work over the past few years has shown that the thalassaemias are caused by many different mutations. In some cases there are major gene deletions or rearrangements, but in most the molecular lesions are more
通过羊膜穿刺术对β-地中海贫血进行产前诊断：使用多个多态性限制性核酸内切酶位点进行连锁分析。
影响因子：
20.3
作者：
KazazianJr,HH;Phillips3rd,JA;Boehm,CD;Vik,TA;Mahoney,MJ;Ritchey,AK
通讯作者：
Ritchey,AK
一种针对镰状细胞性贫血的敏感新产前检测。
DOI：
10.1056/nejm198207013070105
发表时间：
1982
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chang,JC;Kan,YW
通讯作者：
Kan,YW