We report novel mutations in exon 7 of human phenylalanine hydroxylase (PAH) gene of phenylketonuria (PKU ) in southern Chinese, analysed by using PCR-DGGE (denaturing gradient gel electrophoresis ), solid phase DNA s...We report novel mutations in exon 7 of human phenylalanine hydroxylase (PAH) gene of phenylketonuria (PKU ) in southern Chinese, analysed by using PCR-DGGE (denaturing gradient gel electrophoresis ), solid phase DNA sequencing and Ih vliro expression. One of the 2 novel mutations, IVS6nt1, is an intron-exon Junctional mutation which results a splicing defect in mRNA. Arg252Gln is another novel mutation with residual PAH activity only 24 % compared to wild type in in vitro mutagenesis and expression in Cos-1 cell. Other 3 known mutations and polymorphism including Arg241Cys, Arg243Gln and Val245Val(GTG to GTA) together with these novel mutations composed the mutatlonal profile of exon 7 in the PAH gene of PKUs in this populations.展开更多
Exon 7 of the l’henylalan1ne hydroxylase (PAH) gene was analyzed in 15 chlldren affected wlth classicphenylketonL1rla (PKU) from northern Chlna by uslng PCRxsingle strand conformation polymorphism(PCR-SSCP) technique...Exon 7 of the l’henylalan1ne hydroxylase (PAH) gene was analyzed in 15 chlldren affected wlth classicphenylketonL1rla (PKU) from northern Chlna by uslng PCRxsingle strand conformation polymorphism(PCR-SSCP) technique and DNA direct sequencing. Six missense mutatlons (l. e. R2413Q. R 241H, G247V,1,2 19H, F2541;lnd G257V )and one silent rnutatlon (V245v ) were identified. The latter three missense mu-tations were demonstrated as novel mltations in comparison with the PAH mutation database. one missense mt1tation (R241 H) was flrst dowumeTlted in Chinese. our results showed populatlon ancl reglon tllffer-ences in the PAH mutation clistribution. and suggest that there is more thfln one founding population forPKU in China. The fincling of novel mutations will enhence the molecular diagnosis of PKU.展开更多
Phenylketonuria (PKU, MIM 261600) is the most common inborn error of amino acid metabolism. To date, a total of more than 500 mutations have been associated with the disease. In this report, the novel p.Glu182Lys muta...Phenylketonuria (PKU, MIM 261600) is the most common inborn error of amino acid metabolism. To date, a total of more than 500 mutations have been associated with the disease. In this report, the novel p.Glu182Lys mutation, found in a Portuguese family in combination with the previously reported p.Leu 348Val, is presented and its putative deleterious impact discussed.展开更多
文摘We report novel mutations in exon 7 of human phenylalanine hydroxylase (PAH) gene of phenylketonuria (PKU ) in southern Chinese, analysed by using PCR-DGGE (denaturing gradient gel electrophoresis ), solid phase DNA sequencing and Ih vliro expression. One of the 2 novel mutations, IVS6nt1, is an intron-exon Junctional mutation which results a splicing defect in mRNA. Arg252Gln is another novel mutation with residual PAH activity only 24 % compared to wild type in in vitro mutagenesis and expression in Cos-1 cell. Other 3 known mutations and polymorphism including Arg241Cys, Arg243Gln and Val245Val(GTG to GTA) together with these novel mutations composed the mutatlonal profile of exon 7 in the PAH gene of PKUs in this populations.
文摘Exon 7 of the l’henylalan1ne hydroxylase (PAH) gene was analyzed in 15 chlldren affected wlth classicphenylketonL1rla (PKU) from northern Chlna by uslng PCRxsingle strand conformation polymorphism(PCR-SSCP) technique and DNA direct sequencing. Six missense mutatlons (l. e. R2413Q. R 241H, G247V,1,2 19H, F2541;lnd G257V )and one silent rnutatlon (V245v ) were identified. The latter three missense mu-tations were demonstrated as novel mltations in comparison with the PAH mutation database. one missense mt1tation (R241 H) was flrst dowumeTlted in Chinese. our results showed populatlon ancl reglon tllffer-ences in the PAH mutation clistribution. and suggest that there is more thfln one founding population forPKU in China. The fincling of novel mutations will enhence the molecular diagnosis of PKU.
文摘Phenylketonuria (PKU, MIM 261600) is the most common inborn error of amino acid metabolism. To date, a total of more than 500 mutations have been associated with the disease. In this report, the novel p.Glu182Lys mutation, found in a Portuguese family in combination with the previously reported p.Leu 348Val, is presented and its putative deleterious impact discussed.
文摘目的对一个苯丙氨酸羟化酶缺乏症(phenylalanine hydroxylase deficiency,PAHD)家系苯丙氨酸羟化酶(phenylalanine hydroxylase,PAH)基因进行突变位点检测和分析,探讨此家系发病原因。方法采用二代测序技术(next generation sequencing,NGS)和多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)对先证者及其父母的静脉血进行PAH基因组测序和外显子缺失、重复分析。结果先证者找到1个错义突变和1个剪接缺失,分别为:第6外显子c.630T>G和第2外显子c.61-1G>A,这两个变异在人类基因突变数据库(Human Gene Mutation Database,HGMD)中未见报道,根据美国医学遗传学与基因组学学会(America College of Medical Genetics and Genomics,ACMG)指南判定为临床意义未明和疑似致病性变异;信息软件REVEL预测结果为有害和未知。采用MLPA对先证者进行外显子缺失、重复分析显示PAH基因外显子拷贝数未发现异常。结论PAH基因6号外显子c.630T>G和2号外显子c.61-1G>A可能是该PAHD家系的致病突变。
