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dc.contributor.author
Hillert, Alicia
dc.contributor.author
Anikster, Yair
dc.contributor.author
Belanger Quintana, Amaya
dc.contributor.author
Burlina, Alberto
dc.contributor.author
Burton, Barbara K.
dc.contributor.author
Carducci, Carla
dc.contributor.author
Chiesa, Ana Elena
dc.contributor.author
Christodoulou, John
dc.contributor.author
Dordevic, Maja
dc.contributor.author
Desviat, Lourdes R.
dc.contributor.author
Eliyahu, Aviva
dc.contributor.author
Evers, Roeland A.F.
dc.contributor.author
Fajkusova, Lena
dc.contributor.author
Feillet, Francois
dc.contributor.author
Bonfim Freitas, Pedro E.
dc.contributor.author
Gizewska, María
dc.contributor.author
Gundorova, Polina
dc.contributor.author
Karall, Daniela
dc.contributor.author
Kneller, Katya
dc.contributor.author
Kutsev, Sergey I.
dc.contributor.author
Leuzzi, Vincenzo
dc.contributor.author
Levy, Harvey L.
dc.contributor.author
Lichter Koneck, Uta
dc.contributor.author
Muntau, Ania C.
dc.contributor.author
Namour, Fares
dc.contributor.author
Oltarzewsk, Mariusz
dc.contributor.author
Paras, Andrea
dc.contributor.author
Perez, Belén
dc.contributor.author
Polak, Emil
dc.contributor.author
Polyakov, Alexander V.
dc.contributor.author
Porta, Francesco
dc.contributor.author
Rohrbach, Marianne
dc.contributor.author
Scholl Bürgi, Sabine
dc.contributor.author
Spécola, Norma
dc.contributor.author
Stojiljkovic, Maja
dc.contributor.author
Shen, Nan
dc.contributor.author
Santana da Silva, Luiz C.
dc.contributor.author
Skouma, Anastasia
dc.contributor.author
van Spronsen, Francjan
dc.contributor.author
Stoppioni, Vera
dc.contributor.author
Thöny, Beat
dc.contributor.author
Trefz, Friedrich K.
dc.contributor.author
Vockley, Jerry
dc.contributor.author
Yu, Youngguo
dc.contributor.author
Zschocke, Johannes
dc.contributor.author
Hoffmann, Georg F.
dc.contributor.author
Garbade, Sven F.
dc.contributor.author
Blau, Nenad
dc.date.available
2021-10-06T15:06:07Z
dc.date.issued
2020-08
dc.identifier.citation
Hillert, Alicia; Anikster, Yair; Belanger Quintana, Amaya; Burlina, Alberto; Burton, Barbara K.; et al.; The Genetic Landscape and Epidemiology of Phenylketonuria; Cell Press; American Journal Of Human Genetics; 107; 2; 8-2020; 234-250
dc.identifier.issn
0002-9297
dc.identifier.uri
http://hdl.handle.net/11336/142868
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>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>T (p.Arg408Trp) (22.2%), c.1066−11G>A (IVS10−11G>A) (6.4%), and c.782G>A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066−11G>A];[1066−11G>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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Cell Press
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BH4
dc.subject
HYPERPHENYLALANINEMIA
dc.subject
PAH DEFICIENCY
dc.subject
PHENYLALANINE
dc.subject
PKU
dc.subject
TETRAHYDROBIOPTERIN
dc.subject.classification
Epidemiología
dc.subject.classification
Ciencias de la Salud
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
The Genetic Landscape and Epidemiology of Phenylketonuria
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-08-20T19:39:17Z
dc.journal.volume
107
dc.journal.number
2
dc.journal.pagination
234-250
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Hillert, Alicia. No especifíca;
dc.description.fil
Fil: Anikster, Yair. No especifíca;
dc.description.fil
Fil: Belanger Quintana, Amaya. No especifíca;
dc.description.fil
Fil: Burlina, Alberto. No especifíca;
dc.description.fil
Fil: Burton, Barbara K.. No especifíca;
dc.description.fil
Fil: Carducci, Carla. No especifíca;
dc.description.fil
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
dc.description.fil
Fil: Christodoulou, John. No especifíca;
dc.description.fil
Fil: Dordevic, Maja. No especifíca;
dc.description.fil
Fil: Desviat, Lourdes R.. No especifíca;
dc.description.fil
Fil: Eliyahu, Aviva. No especifíca;
dc.description.fil
Fil: Evers, Roeland A.F.. No especifíca;
dc.description.fil
Fil: Fajkusova, Lena. No especifíca;
dc.description.fil
Fil: Feillet, Francois. No especifíca;
dc.description.fil
Fil: Bonfim Freitas, Pedro E.. No especifíca;
dc.description.fil
Fil: Gizewska, María. No especifíca;
dc.description.fil
Fil: Gundorova, Polina. No especifíca;
dc.description.fil
Fil: Karall, Daniela. No especifíca;
dc.description.fil
Fil: Kneller, Katya. No especifíca;
dc.description.fil
Fil: Kutsev, Sergey I.. No especifíca;
dc.description.fil
Fil: Leuzzi, Vincenzo. No especifíca;
dc.description.fil
Fil: Levy, Harvey L.. No especifíca;
dc.description.fil
Fil: Lichter Koneck, Uta. No especifíca;
dc.description.fil
Fil: Muntau, Ania C.. No especifíca;
dc.description.fil
Fil: Namour, Fares. No especifíca;
dc.description.fil
Fil: Oltarzewsk, Mariusz. No especifíca;
dc.description.fil
Fil: Paras, Andrea. No especifíca;
dc.description.fil
Fil: Perez, Belén. No especifíca;
dc.description.fil
Fil: Polak, Emil. No especifíca;
dc.description.fil
Fil: Polyakov, Alexander V.. No especifíca;
dc.description.fil
Fil: Porta, Francesco. No especifíca;
dc.description.fil
Fil: Rohrbach, Marianne. No especifíca;
dc.description.fil
Fil: Scholl Bürgi, Sabine. No especifíca;
dc.description.fil
Fil: Spécola, Norma. No especifíca;
dc.description.fil
Fil: Stojiljkovic, Maja. No especifíca;
dc.description.fil
Fil: Shen, Nan. No especifíca;
dc.description.fil
Fil: Santana da Silva, Luiz C.. No especifíca;
dc.description.fil
Fil: Skouma, Anastasia. No especifíca;
dc.description.fil
Fil: van Spronsen, Francjan. No especifíca;
dc.description.fil
Fil: Stoppioni, Vera. No especifíca;
dc.description.fil
Fil: Thöny, Beat. No especifíca;
dc.description.fil
Fil: Trefz, Friedrich K.. No especifíca;
dc.description.fil
Fil: Vockley, Jerry. No especifíca;
dc.description.fil
Fil: Yu, Youngguo. No especifíca;
dc.description.fil
Fil: Zschocke, Johannes. No especifíca;
dc.description.fil
Fil: Hoffmann, Georg F.. No especifíca;
dc.description.fil
Fil: Garbade, Sven F.. No especifíca;
dc.description.fil
Fil: Blau, Nenad. No especifíca;
dc.journal.title
American Journal Of Human Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ajhg.2020.06.006
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