Wang N, Zhu Y, Xu K, Qiu Z, Song W, Huang S
Department of Biochemistry, Kunming Medical College, Kunming, Yunnan, 650031 P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1999 Feb 10;16(1):9-11.
To identify the mutations of the phenylalanine hydroxylase gene in Yunnan so as to enhance the gene diagnosis of classical phenylketonuria (PKU) in that south-western province of China.
Exons 4,5,6,7,10,11 and 12 of the phenylalanine hydroxylase(PAH) were analyzed in 13/14 children affected with classical PKU from Yunnan by using PCR-single strand conformation polymorphism (PCR-SSCP),PCR-ASO dot blot hybridization,allele specific polymerase chain reaction(ASPCR) and PCR-direct sequencing.
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.
Five kinds of popular PAH gene mutation (R243Q,Y204C,V399V,Y356X and R413P) identified 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.
鉴定云南省苯丙氨酸羟化酶基因的突变情况,以加强对中国西南部该省经典型苯丙酮尿症(PKU)的基因诊断。
采用聚合酶链反应-单链构象多态性(PCR-SSCP)、PCR-ASO斑点杂交、等位基因特异性聚合酶链反应(ASPCR)及PCR直接测序法,对来自云南的13/14例经典型PKU患儿的苯丙氨酸羟化酶(PAH)基因第4、5、6、7、10、11和12外显子进行分析。
鉴定出5种错义突变,即R243Q(5/26)、Y204C(3/28)、G247V(1/26)、R413P(2/28)和T418P(1/28);3种无义突变,即Y166X(C→G)(2/26)、W326X(1/28)和Y356X(2/26);以及1种沉默突变(V399V)(2/26)。与PAH突变数据库相比,无义突变Y166X(C→G)应为新突变。
在云南人群中鉴定出的5种常见PAH基因突变(R243Q、Y204C、V399V、Y356X和R413P)与北方人群相似,但与南方人群不同。这一发现将提高PKU基因诊断的效率,并为PAH突变分布模式的人群和区域差异研究提供参考价值。