Molecular genetics of tetrahydrobiopterin‐responsive phenylalanine hydroxylase deficiency

@article{Zurflh2008MolecularGO,
  title={Molecular genetics of tetrahydrobiopterin‐responsive phenylalanine hydroxylase deficiency},
  author={Marcel R. Zurfl{\"u}h and Johannes Zschocke and Martin Lindner and François Feillet and C{\'e}line Ch{\'e}ry and Alberto B Burlina and Raymond C. Stevens and Beat Th{\"o}ny and Nenad Blau},
  journal={Human Mutation},
  year={2008},
  volume={29}
}
Mutations in the phenylalanine hydroxylase (PAH) gene result in phenylketonuria (PKU. [] Key Method The current project entailed genotype analysis of 315 BH(4)-responsive patients tabulated in the BIOPKUdb database and comparison with the data from the PAHdb locus-specific knowledgebase, as well as with previously published PAH mutations for several European countries, Northern China, and South Korea. We identified 57 mutations, presenting with a substantial residual PAH activity (average approximately 47…

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These results show that BH4 non-responsiveness is associated with genotype, however, patients with mutations in the regulatory domain show inconsistent results.

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A greater understanding of the relationships between individual gene variant, residual PAH activity, tetrahydrobiopterin (BH4) responsiveness, and the clinical PKU phenotype may increase the potential for individualized management of PKU in future.

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Treatment with tetrahydrobiopterin (BH4) is the latest therapeutic option approved for patients with phenylketonuria (PKU)—one of the most frequent inborn metabolic diseases. PKU or phenylalanine

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The first report on the spectrum of PAH variants in Jiangsu province is presented, which identifies one novel PAH variant and tries to show a genotype–phenotype relationship also regarding BH4-responsiveness.

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TLDR
The proportion of phenylketonuria-patients who could benefit from the use of BH4 reaches approximately 10% in the entire region, which is similar percentage of the "BH4-responsive" variants of a PAH gene in patients from other countries of Eastern Europe.

Unresponsiveness to tetrahydrobiopterin of phenylalanine hydroxylase deficiency.

Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria

TLDR
Genotype-based predictions of BH4-responsiveness are only for selecting potential responders and it is necessary to test potential responders with a long-term BH 4 challenge.

Molecular mechanisms of PAH function in response to phenylalanine and tetrahydrobiopterin binding

TLDR
Detailed knowledge on the mechanism of the misfolding-induced loss of function in PAH deficiency enabled a better understanding of the molecular mode of action of pharmacological rescue of enzyme function by BH4.

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness

TLDR
This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations, and highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients.
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TLDR
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TLDR
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