dc.creator | Hillert, Alicia | |
dc.creator | Anikster, Yair | |
dc.creator | Belanger-Quintana, Amaya | |
dc.creator | Burlina, Alberto | |
dc.creator | Burton, Barbara K. | |
dc.creator | Carducci, Carla | |
dc.creator | Chiesa, Ana E. | |
dc.creator | Christodoulou, John | |
dc.creator | Đorđević, Maja | |
dc.creator | Desviat, Lourdes R. | |
dc.creator | Eliyahu, Aviva | |
dc.creator | Evers, Roeland A. F. | |
dc.creator | Fajkusova, Lena | |
dc.creator | Feillet, Francois | |
dc.creator | Bonfim-Freitas, Pedro E. | |
dc.creator | Gizewska, Maria | |
dc.creator | Gundorova, Polina | |
dc.creator | Karall, Daniela | |
dc.creator | Kneller, Katya | |
dc.creator | Kutsev, Sergey, I | |
dc.creator | Leuzzi, Vincenzo | |
dc.creator | Levy, Harvey L. | |
dc.creator | Lichter-Konecki, Uta | |
dc.creator | Muntau, Ania C. | |
dc.creator | Namour, Fares | |
dc.creator | Oltarzewski, Mariusz | |
dc.creator | Paras, Andrea | |
dc.creator | Perez, Belen | |
dc.creator | Polak, Emil | |
dc.creator | Polyakov, Alexander, V | |
dc.creator | Porta, Francesco | |
dc.creator | Rohrbach, Marianne | |
dc.creator | Scholl-Burgi, Sabine | |
dc.creator | Specola, Norma | |
dc.creator | Stojiljković, Maja | |
dc.creator | Shen, Nan | |
dc.creator | Santana-da Silva, Luiz C. | |
dc.creator | Skouma, Anastasia | |
dc.creator | van Spronsen, Francjan | |
dc.creator | Stoppioni, Vera | |
dc.creator | Thony, Beat | |
dc.creator | Trefz, Friedrich K. | |
dc.creator | Vockley, Jerry | |
dc.creator | Yu, Youngguo | |
dc.creator | Zschocke, Johannes | |
dc.creator | Hoffmann, Georg F. | |
dc.creator | Garbade, Sven F. | |
dc.creator | Blau, Nenad | |
dc.date.accessioned | 2022-11-15T15:11:49Z | |
dc.date.available | 2022-11-15T15:11:49Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0002-9297 | |
dc.identifier.uri | https://imagine.imgge.bg.ac.rs/handle/123456789/1314 | |
dc.description.abstract | 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. | en |
dc.publisher | Cell Press, Cambridge | |
dc.relation | Fundacion Isabel Gemio-Fundacion La Caixa [LCF/PR/PR16/11110018] | |
dc.relation | Regional Government of Madrid [B2017/BMD3721] | |
dc.relation | NIH, United States [R01DK117916, R01NR016991] | |
dc.relation | Victorian Government's Operational Infrastructure Support Program | |
dc.relation | Dietmar Hopp Foundation, St. Leon-Rot | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | American Journal of Human Genetics | |
dc.title | The Genetic Landscape and Epidemiology of Phenylketonuria | en |
dc.type | article | |
dc.rights.license | BY | |
dc.citation.epage | 250 | |
dc.citation.issue | 2 | |
dc.citation.other | 107(2): 234-250 | |
dc.citation.rank | aM21 | |
dc.citation.spage | 234 | |
dc.citation.volume | 107 | |
dc.identifier.doi | 10.1016/j.ajhg.2020.06.006 | |
dc.identifier.fulltext | https://imagine.imgge.bg.ac.rs/bitstream/id/81/1311.pdf | |
dc.identifier.pmid | 32668217 | |
dc.identifier.scopus | 2-s2.0-85088865157 | |
dc.identifier.wos | 000558491800006 | |
dc.type.version | publishedVersion | |