Knappskog P M, Eiken H G, Martinez A, Flatmark T, Apold J
Department of Medical Genetics, Haukeland Hospital, Bergen, Norway.
Hum Genet. 1995 Feb;95(2):171-3. doi: 10.1007/BF00209396.
The mutation S349P in exon 10 of the phenylalanine hydroxylase (PAH) gene was identified in one Norwegian and one Polish phenylketonuria (PKU) allele on a haplotype 1.7 background. This missense mutation in PAH codon 349 is a T to C transition in cDNA position 1267. This mutation has been reported both on haplotype 1 and 4, suggesting recurrent mutation. In two different expression systems, the pET and the pMAL systems of Escherichia coli, it was shown that the S349P mutation, introduced by site directed mutagenesis, results in complete loss of enzymatic activity. Thus, protein instability alone does not seem to be the direct cause of the lack of activity of this PKU mutation as previously reported.
在一名挪威人和一名波兰人的苯丙酮尿症（PKU）等位基因中，于单倍型1.7背景下鉴定出苯丙氨酸羟化酶（PAH）基因第10外显子中的S349P突变。PAH密码子349处的这种错义突变是cDNA位置1267处的T到C转换。该突变已在单倍型1和4上均有报道，提示存在反复突变。在两种不同的表达系统，即大肠杆菌的pET和pMAL系统中，研究表明通过定点诱变引入的S349P突变会导致酶活性完全丧失。因此，如先前报道的那样，单独的蛋白质不稳定性似乎并非该PKU突变缺乏活性的直接原因。
