Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria in Shaanxi, China

Wang, Lin; Wang, Xiaobin; He, Bin; Cai, Na; Li, Wei; Lou, Chao; Xin, Shuwen; Wu, Qiuhua; Yu, Wenbin; Qiang, Rong

doi:10.1515/jpem-2016-0448

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…Three pathogenic mutations in a proband were detected in two of our probands. One carried c. reported previously [9,10]. The genotype of 3 pathogenic mutations in a patient is not uncommon, for an example, a total 35 PKU patients with this genotype were detected from 796 PKU patients by nextgeneration sequencing [3].…”

Section: Spectrum Of Mutations In Pah Genementioning

confidence: 99%

Molecular diagnosis of Phenylketonuria in 157 Families and Prenatal Diagnosis of Phenylketonuria

Xiao¹,

Gu²,

Wu³

et al. 2019

Preprint

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Background Phenylketonuria (PKU) is a genetic metabolic disease with a relatively higher incidence, but only a few studies about the prenatal diagnosis of PKU have been reported so far in China. The aim of this study was to characterize the spectrum of mutations in PAH gene in PKU probands and the prenatal diagnosis of PKU in north China.Methods A total of 157 families in which PKU patients had been diagnosed were included in the study. The 13 exons and their flanking sequences of PAH gene were amplified by PCR and sequenced in the probands. If none or only one mutant allele was found in the probands, the sample was subjected to MLPA for large deletions/duplication detection in PAH gene. Prenatal diagnosis was performed for pregnant women in these families.Results Pathogenic mutation in PAH was found in 2 alleles in 148 probands and in one allele in 7 probands, and the mutation was not detected in 2 probands. There were 289 point mutants, 10 frame-shift mutations and 4 large deletions with a total of 80 kinds of mutations. The most prevalent mutations were R243Q (17.2%), EX6-96A>G (8.6%) and V399V (8.0%). We also found a novel mutation of 163_164insATAT. Prenatal diagnosis of 95 families found 21 healthy fetus (20.4%), 52 carriers (50.5%) and 30 patients (29.1%), and the accuracy of prenatal diagnosis was confirmed after birth of the fetuses.Conclusion We present here a spectrum of mutations in PAH gene in PKU patients in north China. Prenatal diagnosis for PKU is useful for PKU families to prevent birth of another PKU case.

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Section: Spectrum Of Mutations In Pah Genementioning

confidence: 99%

Molecular diagnosis of Phenylketonuria in 157 Families and Prenatal Diagnosis of Phenylketonuria

Xiao¹,

Gu²,

Wu³

et al. 2019

Preprint

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Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria

Wang

Jin

et al. 2022

Journal of Pediatric Endocrinology and Metabolism

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Objectives Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism. It is mainly caused by a deficiency in phenylalanine hydroxylase (PAH) and frequently diagnosed with Sanger sequencing. To some extent, allelic dropout can explain the inconsistency in genotype and phenotype. Methods Three families were evaluated through DNA sequence analysis, multiplex ligation-dependent probe amplification (MLPA) and prenatal diagnosis technologies. The possibility of inconsistency in phenotype and genotype with c.331C>T variant was analysed. Results Through pedigree analysis, three mothers carried a homozygous c.331C>T variant, which was a false-positive result. New primers were used, and this error was caused by allelic dropout. In this case, c.158G>A was likely a benign variant. Conclusions Sequence variants in primer-binding regions could cause allelic dropout, creating unpredictable errors in genotyping. Our results emphasised the need for careful measures to treat genotype–phenotype inconsistencies.

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Clinical Implementation of Expanded Carrier Screening in Pregnant Women at Early Gestational Weeks: A Chinese Cohort Study

Shi

Liauw

Tong

et al. 2021

Genes

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Demands for expanded carrier screening (ECS) are growing and ECS is becoming an important part of obstetrics practice and reproductive planning. The aim of this study is to evaluate the feasibility of a small-size ECS panel in clinical implementation and investigate Chinese couples’ attitudes towards ECS. An ECS panel containing 11 recessive conditions was offered to Chinese pregnant women below 16 gestational weeks. Sequential testing of their partners was recommended for women with a positive carrier status. The reproductive decision and pregnancy outcome were surveyed for at-risk couples. A total of 1321 women performed ECS successfully and the overall carrier rate was 19.23%. The estimated at-risk couple rate was 0.83%. Sequential testing was performed in less than half of male partners. Eight at-risk couples were identified and four of them performed prenatal diagnosis. Our study demonstrated that a small-size ECS panel could yield comparable clinical value to a larger-size panel when the carrier rate of the individual condition is equal or greater than 1%. In addition, more than half of male partners whose wives were carriers declined any types of sequential testing possibly due to a lack of awareness and knowledge of genetic disorders. Genetic education is warranted for the better implementation of ECS.

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Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria in Shaanxi, China

Abstract: PAH gene analysis is a crucial method for PKU diagnosis and prenatal genetic prognosis, even though many uncommon mutations would affect the analysis and diagnosis of genetic abnormalities.

Cited by 3 publications

References 19 publications

Molecular diagnosis of Phenylketonuria in 157 Families and Prenatal Diagnosis of Phenylketonuria

Molecular diagnosis of Phenylketonuria in 157 Families and Prenatal Diagnosis of Phenylketonuria

Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria

Clinical Implementation of Expanded Carrier Screening in Pregnant Women at Early Gestational Weeks: A Chinese Cohort Study

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