The Genetic Landscape and Epidemiology of Phenylketonuria

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAM

Detalles Bibliográficos
Autores: Hillert, Alicia, Ruiz Desviat, Lourdes, Pérez González, María Belén
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/709213
Acceso en línea:http://hdl.handle.net/10486/709213
https://dx.doi.org/10.1016/j.ajhg.2020.06.006
Access Level:acceso abierto
Palabra clave:PKU
hyperphenylalaninemia
PAH deficiency
tetrahydrobiopterin
BH4
phenylalanine
Biología y Biomedicina / Biología
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spelling The Genetic Landscape and Epidemiology of PhenylketonuriaHillert, AliciaRuiz Desviat, LourdesPérez González, María BelénPKUhyperphenylalaninemiaPAH deficiencytetrahydrobiopterinBH4phenylalanineBiología y Biomedicina / BiologíaArtículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMPhenylketonuria (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 outcomeThis work was funded in part by the Fundacio´n Isabel Gemio-Fundacion La Caixa (LCF/PR/PR16/11110018), the Regional Government of Madrid (CAM, B2017/BMD3721), and by NIH, United States grants R01DK117916 and R01NR016991.Cell PressDepartamento de Biología MolecularFacultad de Ciencias20202020-07-14research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/709213https://dx.doi.org/10.1016/j.ajhg.2020.06.006reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7092132026-06-23T12:46:27Z
dc.title.none.fl_str_mv The Genetic Landscape and Epidemiology of Phenylketonuria
title The Genetic Landscape and Epidemiology of Phenylketonuria
spellingShingle The Genetic Landscape and Epidemiology of Phenylketonuria
Hillert, Alicia
PKU
hyperphenylalaninemia
PAH deficiency
tetrahydrobiopterin
BH4
phenylalanine
Biología y Biomedicina / Biología
title_short The Genetic Landscape and Epidemiology of Phenylketonuria
title_full The Genetic Landscape and Epidemiology of Phenylketonuria
title_fullStr The Genetic Landscape and Epidemiology of Phenylketonuria
title_full_unstemmed The Genetic Landscape and Epidemiology of Phenylketonuria
title_sort The Genetic Landscape and Epidemiology of Phenylketonuria
dc.creator.none.fl_str_mv Hillert, Alicia
Ruiz Desviat, Lourdes
Pérez González, María Belén
author Hillert, Alicia
author_facet Hillert, Alicia
Ruiz Desviat, Lourdes
Pérez González, María Belén
author_role author
author2 Ruiz Desviat, Lourdes
Pérez González, María Belén
author2_role author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv PKU
hyperphenylalaninemia
PAH deficiency
tetrahydrobiopterin
BH4
phenylalanine
Biología y Biomedicina / Biología
topic PKU
hyperphenylalaninemia
PAH deficiency
tetrahydrobiopterin
BH4
phenylalanine
Biología y Biomedicina / Biología
description Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAM
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-07-14
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/709213
https://dx.doi.org/10.1016/j.ajhg.2020.06.006
url http://hdl.handle.net/10486/709213
https://dx.doi.org/10.1016/j.ajhg.2020.06.006
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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