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)is an autosomal recessive metabolic disorder caused by deficiency of phenylalanine hydroxylase(PAH).The major molecular defects causing PKU are missense mutations of PAH gene.Large deletions of exo...Phenylketonuria(PKU)is an autosomal recessive metabolic disorder caused by deficiency of phenylalanine hydroxylase(PAH).The major molecular defects causing PKU are missense mutations of PAH gene.Large deletions of exon 5(EX5del955 and EX5del4232ins)were first reported by the Czech study and were later found also in the Polish,Slovak,Slovenian and Italian PKU-patients.These observations demonstrate the existence of a common subset of this mutation predominantly among Central European populations of Slavic descent.That is why we suggest that EX5del1955 and EX5del4232ins268 mutations might be frequent causes of PKU in Ukrainian patients.EX5del955 and EX5del4232ins268 mutations were analyzed in 106 unrelated PKU patients negative for PAH gene mutations on one or both alleles from our previous analysis.The simultaneous detection of EX5del4232ins268 and EX5del955 mutations was performed by PCR amplification of mutant alleles.EX5del955 mutation was not detected in the Ukrainian patients.This relative alleles frequency of EX5del4232ins268 mutation in the Ukrainian PKU population was determined as 1,66%.Our findings can be the one more evidence of Central European Slavic origin of EX5del4232ins268 mutation,suggested previously.This finding is important for the improvement of DNA diagnosis necessary for the management of PKU patients from Ukraine.展开更多
A silent mutation or sequence polymorphism, A to T substitution at codon 399 in exon11 of the PAH gene from a Chinese PKU patient, was found by sequence analysis. The fre-quencies of this new mutation in normal and ab...A silent mutation or sequence polymorphism, A to T substitution at codon 399 in exon11 of the PAH gene from a Chinese PKU patient, was found by sequence analysis. The fre-quencies of this new mutation in normal and abnormal (PKU) genes were 0.005 and 0.09,respectively, based on the analyses of 100 normal individuals and 39 PKU patients usingDNA amplification with polymerase chain reaction (PCR) and oligonucleotide hybridizationmethods. This silent mutation can be used as a "genetic marker" for PKU prenatal diagno-sis. Recently, a fetus at risk for PKU, who could not be completely predicted by RFLPslinkage analysis, was prenatally diagnosed with this genetic marker.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.
基金We cordially thank all PKU families who participated in this study.This study was supported by a grant from the National Academy of Science of Ukraine(no.0115U003747).
文摘Phenylketonuria(PKU)is an autosomal recessive metabolic disorder caused by deficiency of phenylalanine hydroxylase(PAH).The major molecular defects causing PKU are missense mutations of PAH gene.Large deletions of exon 5(EX5del955 and EX5del4232ins)were first reported by the Czech study and were later found also in the Polish,Slovak,Slovenian and Italian PKU-patients.These observations demonstrate the existence of a common subset of this mutation predominantly among Central European populations of Slavic descent.That is why we suggest that EX5del1955 and EX5del4232ins268 mutations might be frequent causes of PKU in Ukrainian patients.EX5del955 and EX5del4232ins268 mutations were analyzed in 106 unrelated PKU patients negative for PAH gene mutations on one or both alleles from our previous analysis.The simultaneous detection of EX5del4232ins268 and EX5del955 mutations was performed by PCR amplification of mutant alleles.EX5del955 mutation was not detected in the Ukrainian patients.This relative alleles frequency of EX5del4232ins268 mutation in the Ukrainian PKU population was determined as 1,66%.Our findings can be the one more evidence of Central European Slavic origin of EX5del4232ins268 mutation,suggested previously.This finding is important for the improvement of DNA diagnosis necessary for the management of PKU patients from Ukraine.
文摘A silent mutation or sequence polymorphism, A to T substitution at codon 399 in exon11 of the PAH gene from a Chinese PKU patient, was found by sequence analysis. The fre-quencies of this new mutation in normal and abnormal (PKU) genes were 0.005 and 0.09,respectively, based on the analyses of 100 normal individuals and 39 PKU patients usingDNA amplification with polymerase chain reaction (PCR) and oligonucleotide hybridizationmethods. This silent mutation can be used as a "genetic marker" for PKU prenatal diagno-sis. Recently, a fetus at risk for PKU, who could not be completely predicted by RFLPslinkage analysis, was prenatally diagnosed with this genetic marker.
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.
