Kazazian H H
Clin Chem. 1985 Sep;31(9):1509-13.
Gene probes can now be used to detect a variety of mutations that produce single-gene disorders. In present clinical practice, restriction endonuclease analysis is used for the prenatal diagnosis of sickle cell anemia, alpha-thalassemia, and beta-thalassemia. Direct detection of the mutation is possible in alpha-thalassemia, where a deletion has usually occurred, and in sickle cell anemia, where the mutation alters the recognition sequence of the restriction endonuclease, Mst II. Indirect detection of beta-thalassemia is based on using normal variations in DNA (DNA polymorphisms) to track normal and affected beta-globin genes in families. This latter kind of analysis is also useful in detecting the phenylalanine hydroxylase genes affected in phenylketonuria and will often be used in disorders where the mutations are unknown. In cases where the mutation is known, direct analysis by use of oligonucleotide probes is a new and important advance. An example of this type of gene detection in a family with classical hemophilia is presented. In addition, with chorion villus biopsy, detection of these inherited diseases is feasible by the 12th week of pregnancy.
基因探针现在可用于检测导致单基因疾病的多种突变。在目前的临床实践中，限制性内切酶分析用于镰状细胞贫血、α地中海贫血和β地中海贫血的产前诊断。在α地中海贫血（通常发生了缺失）和镰状细胞贫血（突变改变了限制性内切酶Mst II的识别序列）中，可以直接检测到突变。β地中海贫血的间接检测是基于利用DNA中的正常变异（DNA多态性）来追踪家族中正常和受影响的β珠蛋白基因。后一种分析方法在检测苯丙酮尿症中受影响的苯丙氨酸羟化酶基因时也很有用，并且经常用于突变未知的疾病。在已知突变的情况下，使用寡核苷酸探针进行直接分析是一项新的重要进展。本文给出了一个在患有经典血友病的家族中进行此类基因检测的例子。此外，通过绒毛膜绒毛取样，在怀孕第12周时就可以检测出这些遗传性疾病。
