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The Genetic Landscape and Epidemiology of Phenylketonuria

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F20%3A00072930" target="_blank" >RIV/65269705:_____/20:00072930 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/abs/pii/S0002929720301944" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0002929720301944</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.ajhg.2020.06.006" target="_blank" >10.1016/j.ajhg.2020.06.006</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    The Genetic Landscape and Epidemiology of Phenylketonuria

  • Original language description

    Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A&gt;G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C&gt;T (p.Arg408Trp) (22.2%), c.1066-11G&gt;A (IVS10-11G&gt;A) (6.4%), and c.782G&gt;A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G&gt;A];[1066-11G&gt;A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10603 - Genetics and heredity (medical genetics to be 3)

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2020

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    American journal of human genetics

  • ISSN

    0002-9297

  • e-ISSN

  • Volume of the periodical

    107

  • Issue of the periodical within the volume

    2

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    17

  • Pages from-to

    234-250

  • UT code for WoS article

    000558491800006

  • EID of the result in the Scopus database

    2-s2.0-85088865157