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@article{1094897,
author = {Réblová, Kamila and Hrubá, Zuzana and Procházková, Dagmar and Pazdírková, Renata and Pouchlá, Slávka and Fajkusová, Lenka},
article_location = {Amsterdam},
article_number = {APR 18},
doi = {http://dx.doi.org/10.1016/j.cca.2013.01.006},
keywords = {Hyperphenylalaninemia; molecular modelling; phenylalanine hydroxylase},
language = {eng},
issn = {0009-8981},
journal = {Clinica Chimica Acta},
title = {Hyperphenylalaninemia in the Czech Republic: Genotype-phenotype correlations and in silico analysis of novel missense mutations},
url = {http://www.sciencedirect.com/science/article/pii/S0009898113000211},
volume = {419},
year = {2013}
}
TY - JOUR
ID - 1094897
AU - Réblová, Kamila - Hrubá, Zuzana - Procházková, Dagmar - Pazdírková, Renata - Pouchlá, Slávka - Fajkusová, Lenka
PY - 2013
TI - Hyperphenylalaninemia in the Czech Republic: Genotype-phenotype correlations and in silico analysis of novel missense mutations
JF - Clinica Chimica Acta
VL - 419
IS - APR 18
SP - 1-10
EP - 1-10
PB - Elsevier Science BV
SN - 00098981
KW - Hyperphenylalaninemia
KW - molecular modelling
KW - phenylalanine hydroxylase
UR - http://www.sciencedirect.com/science/article/pii/S0009898113000211
L2 - http://www.sciencedirect.com/science/article/pii/S0009898113000211
N2 - Abstract BACKGROUND: Hyperphenylalaninemia (HPA) is one of the most common inherited metabolic disorders caused by deficiency of the enzyme phenylalanine hydroxylase (PAH). HPA is associated with mutations in the PAH gene, which leads to reduced protein stability and/or impaired catalytic function. Currently, almost 700 different disease-causing mutations have been described. The impact of mutations on enzyme activity varies ranging from classical PKU, mild PKU, to non-PKU HPA phenotype. METHODS: We provide results of molecular genetic diagnostics of 665 Czech unrelated HPA patients, structural analysis of missense mutations associated with classical PKU and non-PKU HPA phenotype, and prediction of effects of 6 newly discovered HPA missense mutations using bioinformatic approaches and Molecular Dynamics simulations. RESULTS: Ninety-eight different types of mutations were indentified. Thirteen of these were novel (6 missense, 2 nonsense, 1 splicing, and 4 small gene rearrangements). Structural analysis revealed that classical PKU mutations are more non-conservative compared to non-PKU HPA mutations and that specific sequence and structural characteristics of a mutation might be critical when distinguishing between non-PKU HPA and classical PKU mutations. The greatest impact was predicted for the p.(Phe263Ser) mutation while other novel mutations p.(Asn167Tyr), p.(Thr200Asn), p.(Asp229Gly), p.(Leu358Phe), and p.(Ile406Met) were found to be less deleterious
ER -
RÉBLOVÁ, Kamila, Zuzana HRUBÁ, Dagmar PROCHÁZKOVÁ, Renata PAZDÍRKOVÁ, Slávka POUCHLÁ and Lenka FAJKUSOVÁ. Hyperphenylalaninemia in the Czech Republic: Genotype-phenotype correlations and in silico analysis of novel missense mutations. \textit{Clinica Chimica Acta}. Amsterdam: Elsevier Science BV, 2013, vol.~419, APR 18, p.~1-10. ISSN~0009-8981. doi:10.1016/j.cca.2013.01.006.
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