Background:Phenylketonuria(PKU)is caused by a defect in phenylalanine hydroxylase(PAH).More than 500 mutations have been reported for the gene encoding PAH.However,approximately l%-5%of these include large deletions a...Background:Phenylketonuria(PKU)is caused by a defect in phenylalanine hydroxylase(PAH).More than 500 mutations have been reported for the gene encoding PAH.However,approximately l%-5%of these include large deletions and large duplications that cannot be detected by conventional methods.Methods:In this report we tried to fully characterize a PAH-deficient patient.The patient was a 2-year-old Japanese boy who was diagnosed with classical PKU at the time of neonatal screening,which was confirmed by the tetrahydrobiopterin-loading test.PCR-related direct sequencing and multiplex ligation-dependent probe amplification(MLPA)were used to analyze of the PAH of the patient.Results:Using PCR-related direct sequencing method,we could detect only a heterozygous novel missense mutation:p.136G>C(p.G46R).A second mutation was detected by MLPA.The patient was heterozygous for a novel large deletion of exons 12 and 13:c.1200-?_1359+?del(EX12_13del).For genetic counseling,an accurate genetic diagnosis is often necessary.Conclusions:Through a combination of MLPA and conventional methods,the success rate of PAH mutation identification can be close to 100%.展开更多
文摘Background:Phenylketonuria(PKU)is caused by a defect in phenylalanine hydroxylase(PAH).More than 500 mutations have been reported for the gene encoding PAH.However,approximately l%-5%of these include large deletions and large duplications that cannot be detected by conventional methods.Methods:In this report we tried to fully characterize a PAH-deficient patient.The patient was a 2-year-old Japanese boy who was diagnosed with classical PKU at the time of neonatal screening,which was confirmed by the tetrahydrobiopterin-loading test.PCR-related direct sequencing and multiplex ligation-dependent probe amplification(MLPA)were used to analyze of the PAH of the patient.Results:Using PCR-related direct sequencing method,we could detect only a heterozygous novel missense mutation:p.136G>C(p.G46R).A second mutation was detected by MLPA.The patient was heterozygous for a novel large deletion of exons 12 and 13:c.1200-?_1359+?del(EX12_13del).For genetic counseling,an accurate genetic diagnosis is often necessary.Conclusions:Through a combination of MLPA and conventional methods,the success rate of PAH mutation identification can be close to 100%.
