Wang T, Okano Y, Eisensmith R C, Fekete G, Schuler D, Berencsi G, Nasz I, Woo S L
Howard Hughes Medical Institute, Department of Cell Biology, Houston, Texas.
Somat Cell Mol Genet. 1990 Jan;16(1):85-90. doi: 10.1007/BF01650483.
Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenylalanine hydroxylase (PAH). Several mutations in the PAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of the PAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg243 to a termination codon, and the mutant allele is associated with haplotype 4 of the PAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe.
苯丙酮尿症（PKU）是一种由于肝脏苯丙氨酸羟化酶（PAH）缺乏引起的遗传性疾病。最近报道了PAH基因中的几种突变，并且在限制性片段长度多态性（RFLP）单倍型与特定突变之间观察到连锁不平衡。通过对PCR扩增的DNA进行直接测序，在一名匈牙利PKU患者的PAH基因第7外显子中鉴定出一种新的分子病变。C到T的转变导致Arg243被终止密码子取代，并且突变等位基因与PAH基因的单倍型4相关。该突变存在于东欧人中九个突变单倍型4等位基因中的两个，而在西欧人和亚洲人中不存在。这种突变等位基因的罕见性及其有限的地理分布表明，该突变事件最近发生在东欧正常的单倍型4背景上。
