Okano Y, Eisensmith R C, Dasovich M, Wang T, Güttler F, Woo S L
Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
Eur J Pediatr. 1991 Mar;150(5):347-52. doi: 10.1007/BF01955938.
A missense mutation has been identified in the phenylalanine hydroxylase (PAH) gene of a Danish patient with hyperphenylalaninaemia (HPA). An A-to-G transition at the second base of codon 414 results in the substitution of Cys for Tyr in the mutant PAH protein. In in vitro expression studies, the Tyr414-to-Cys414 mutant construct produced a protein which exhibited a significant amount of normal PAH enzyme activity, which is consistent with both in vitro and in vivo measurements of PAH activity in HPA patients. Population genetic studies reveal that this mutation is present on 50% of mutant haplotype 4 chromosomes in the Danish population. Together with the previously reported codon 158 mutation, these two mutant alleles comprise over 90% of all mutant haplotype 4 chromosomes in the Northern European population. Thus, two allele-specific oligonucleotide probes can detect most mutant haplotype 4 chromosomes in Northern Europe.
在一名患有高苯丙氨酸血症（HPA）的丹麦患者的苯丙氨酸羟化酶（PAH）基因中发现了一个错义突变。密码子414第二个碱基处的A到G转换导致突变型PAH蛋白中的酪氨酸被半胱氨酸取代。在体外表达研究中，Tyr414-to-Cys414突变体构建体产生了一种具有大量正常PAH酶活性的蛋白质，这与HPA患者PAH活性的体外和体内测量结果一致。群体遗传学研究表明，在丹麦人群中，该突变存在于50%的突变单倍型4染色体上。与先前报道的密码子158突变一起，这两个突变等位基因占北欧人群所有突变单倍型4染色体的90%以上。因此，两种等位基因特异性寡核苷酸探针可以检测出北欧大多数突变单倍型4染色体。
