Trefz F K, Lichter-Konecki U, Krawczak M, Schmidtke J, Dueck M, Nützenadel W, Konecki D S
Universitäts-Kinderklinik Heidelberg.
Monatsschr Kinderheilkd. 1989 Apr;137(4):201-7.
In 170 inherited diseases there exists the possibility for diagnosis at the DNA level. Using phenylketonuria (PKU) and cystic fibrosis (CF) as examples we demonstrate the capability of direct and indirect DNA-diagnosis through the use of DNA markers and allelespecific oligonucleotide hybridization respectively. In 88% of our PKU-patients and in 98% of the CF-patients DNA linkage analysis and therefore prenatal diagnosis on the DNA level can be carried out in affected families. The reliability of DNA-diagnosis is 99.0% for PKU and between 96.0-99.99% for CF depending on where the DNA-markers are localized. In contrast to CF, the PKU gene has been isolated and distinct mutations within the phenylalanine hydroxylase gene have been characterized. There is evidence for a correlation between genotype and clinical and biochemical phenotype. Also in CF it is indicated that certain DNA haplotypes correlate with the severity of the disease: less frequent haplotypes seem to be more often associated with a milder course than haplotype "B/B" which represents 85% of the CF chromosomes. Therefore DNA diagnostic methods not only make a major contribution to improved genetic counseling but also offer the possibility for a better future understanding of the heterogeneity of genetic diseases.
在170种遗传性疾病中，存在在DNA水平进行诊断的可能性。以苯丙酮尿症（PKU）和囊性纤维化（CF）为例，我们分别展示了通过使用DNA标记和等位基因特异性寡核苷酸杂交进行直接和间接DNA诊断的能力。在我们88%的PKU患者和98%的CF患者中，可以在受影响的家庭中进行DNA连锁分析，从而在DNA水平进行产前诊断。PKU的DNA诊断可靠性为99.0%，CF的DNA诊断可靠性在96.0 - 99.99%之间，这取决于DNA标记的定位位置。与CF不同，PKU基因已被分离，并且苯丙氨酸羟化酶基因内的不同突变已被鉴定。有证据表明基因型与临床和生化表型之间存在相关性。在CF中也表明，某些DNA单倍型与疾病的严重程度相关：与代表85%的CF染色体的单倍型“B/B”相比，不太常见的单倍型似乎更常与较轻的病程相关。因此，DNA诊断方法不仅对改善遗传咨询做出了重大贡献，而且为未来更好地理解遗传疾病的异质性提供了可能性。
