云南苯丙氨酸羟化酶基因点突变及外显子5内新突变Y166X(C→G)的鉴定  

Identification of Mutations in the Phenylalanine Hydroxylase Gene and Exon 5 Novel Mutation Y166X (C→G) in Yunnan

作　　者：汪宁[1,2] 朱月春[1,2] 徐葵 邱志明[1,2] 宋文凤 黄尚志[1,2] 

机构地区：[1]昆明医学院生物化学教研室 [2]中国医学科学院基础所医学遗传室

出　　处：《中华医学遗传学杂志》1999年第1期9-11,共3页Chinese Journal of Medical Genetics

基　　金：云南省应用基础研究基金

摘　　要：目的研究云南苯丙氨酸羟化酶基因点突变分布概况，以提高该地区苯丙酮尿症（ＰＫＵ）的基因诊断率。方法应用ＰＣＲ－ＡＳＯ探针斑点杂交，ＰＣＲ－ＳＳＣＰ、ＡＳＰＣＲ和ＤＮＡ直接测序等技术，对１３／１４名云南籍ＰＫＵ患儿的苯丙氨酸羟化酶（ＰＡＨ）基因外显子４、５、６、７、１０、１１和１２进行了鉴定分析。结果共检出５种错义突变：Ｒ２４３Ｑ（５／２６）、Ｙ２０４Ｃ（３／２８）、Ｒ４１３Ｐ（２／２８）、Ｔ４１８Ｐ（１／２８）及Ｇ２４７Ｖ（１／２６），３种无义突变Ｙ１６６Ｘ（Ｃ→Ｇ）（２／２６）、Ｗ３２６Ｘ（１／２８）及Ｙ３５６Ｘ（２／２６）和１种静止突变Ｖ３９９Ｖ（２／２６）。经检索国际ＰＡＨ基因突变数据库，其中Ｙ１６６Ｘ（Ｃ→Ｇ）为首次发现的新突变。结论云南藉ＰＫＵ与中国北方人群有相类似的最常见的ＰＡＨ基因突变类型（Ｒ２４３Ｑ、Ｙ２０４Ｃ、Ｙ３５６Ｘ、Ｖ３９９Ｖ和Ｒ４１３Ｐ），但与南方人群ＰＡＨ基因突变特点则不同。该发现有助于提高云南ＰＫＵ的基因诊断率，并对我国ＰＡＨ基因突变不同地区及人群的分布、起源研究有参考价值。Objective To identify the mutations of the phenylalanine hydroxylase gene in Yunnan so as to enhance the gene diagnosis of classcial phenylketonuria (PKU) in that south western province of China. Methods Exons 4,5,6,7,10,11 and 12 of the phenylalanie hydroxylase (PAH) were analyzed in 13/14 children affected with classical PKU from Yunnan by using PCR single strand conformation polymophism (PCR SSCP), PCR ASO dot blot hybridization, allele spectific polymearse chain reaction (ASPCR) and PCR driect sequencing. Results Five missense mutations, i.e. R243Q (5/26), Y204C(3/28), G247V(1/26), R413P(2/28) and T418P(1/28); three nonsense mutations, i.e. Y166X (C→G) (2/26), W326X(1/28) and Y356X(2/26); and one silent mutation (V399V) (2/26) were identified. The nonsense mutation Y166X(C→G) should be a novel mutation as compared with the PAH Mutation Database.Conclusion Five kinds of popular PAH gene mutation (R243Q, Y204C, V399V, Y356X and R413P) indentified in the people of Yunnan are similar to those in the northern people, but such characteristic is different from that in the southern people. This finding will enhance the efficacy in gene diagnosis of PKU and will be of reference value for studies of population and regional difference in the pattern of PAH mutation distribution.

关 键 词：苯丙酮尿症 苯丙氨酸羟化酶 基因突变 遗传病 

分 类 号：R596.1[医药卫生—内科学] R589.302[医药卫生—临床医学]