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. 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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Basic information
Original name Hyperphenylalaninemia in the Czech Republic: Genotype-phenotype correlations and in silico analysis of novel missense mutations
Name in Czech Hyperfenylalninémie v České republice, korelace genotyp a fenotyp a silico analýza nových missense mutací
Authors RÉBLOVÁ, Kamila (203 Czech Republic, guarantor, belonging to the institution), Zuzana HRUBÁ (203 Czech Republic), Dagmar PROCHÁZKOVÁ (203 Czech Republic, belonging to the institution), Renata PAZDÍRKOVÁ (203 Czech Republic), Slávka POUCHLÁ (203 Czech Republic) and Lenka FAJKUSOVÁ (203 Czech Republic, belonging to the institution).
Edition Clinica Chimica Acta, Amsterdam, Elsevier Science BV, 2013, 0009-8981.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher Netherlands
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 2.764
RIV identification code RIV/00216224:14740/13:00068049
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.1016/j.cca.2013.01.006
UT WoS 000318192700001
Keywords (in Czech) hyperfenylalninémie, molekulární modelování, fenylalanin hydroxylaza
Keywords in English Hyperphenylalaninemia; molecular modelling; phenylalanine hydroxylase
Tags ok, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Olga Křížová, učo 56639. Changed: 22. 1. 2014 11:23.
Abstract
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
Abstract (in Czech)
HPA je jednou z nejčastějších dědičných poruch metabolizmu, způsobená poruchou enzymu PAH v játrech. HPA je spojena s mutacemi s PAH genu, kterých je nyní známo více než 700. HPA se dle zbytkové aktivity enzymu dělí na klasickou PKU, mírnou PKU a non-PKU HPA. Autoři vyšetřeli 665 pacientů s českých rodin. Provedli strukturální analýzu 6 missense mutací za použití bioinformatického přístupu a molekulárně dynamické simulace. Odhalili 98 typů mutací z toho 13 dosud nepopsaných.
Links
ED1.1.00/02.0068, research and development projectName: CEITEC - central european institute of technology
EE2.3.20.0045, research and development projectName: Podpora profesního růstu a mezinárodní integrace výzkumných týmů v oblasti molekulární medicíny
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