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苯丙酮尿症(phenylketonuria,PKU)是一种可以造成儿童不同程度智力损害的常见的先天代谢性疾病,属于常染色体隐性遗传,OMIM编号为261600。PKU是由苯丙氨酸羟化酶(Phenylalanine hydroxylase,PAH)基因突变导致的肝脏PAH酶活性降低或丧失所致,1934年由Folling首先报道了此病。1983年该基因被定位在12q22-24.2。近些年,随着分子遗传学及生物学等科学的发展,对PKU研究也在不断深入。目前在国际PAH数据库(http//www.pahdb.mcgill.ca)中总共收录546种突变等位基因,659种基因型。PKU表型与基因突变类型有关,但是有些带有相同pah基因突变的不同PKU患者存在表型差异。全面了解pah基因结构、pah基因表达特点、酶结构和功能以及基因突变对酶结构和功能的影响的分子机制是对PKU表型认识的基础。本文根据近年来的研究成果,对pah基因结构,PAH酶结构,基因突变及其与表型的关系等进行详细阐述。
Phenylketonuria (PKU) is a common inborn metabolic disorder that can cause mental retardation in children with varying degrees. It belongs to autosomal recessive inheritance (OMIM number: 261600). PKU is caused by a decrease or loss of hepatic PAH enzyme activity caused by mutations of the phenylalanine hydroxylase (PAH) gene, which was first reported by Folling in 1934. In 1983 the gene was located at 12q22-24.2. In recent years, with the development of science such as molecular genetics and biology, the research on PKU is also going deeper and deeper. A total of 546 mutant alleles and 659 genotypes are now included in the International PAH Database (http // www.pahdb.mcgill.ca). The PKU phenotype is related to the type of gene mutation, but there are phenotypic differences in some PKU patients with the same pah gene mutation. A comprehensive understanding of the pah gene structure, pah gene expression characteristics, enzyme structure and function, as well as the molecular mechanism of gene mutation on the structure and function of the enzyme is the basis of understanding PKU phenotype. In this paper, based on recent research results, pah gene structure, PAH enzyme structure, gene mutation and its relationship with the phenotype and so on.