TY  - JOUR
AU  - Hillert, Alicia
AU  - Anikster, Yair
AU  - Belanger-Quintana, Amaya
AU  - Burlina, Alberto
AU  - Burton, Barbara K.
AU  - Carducci, Carla
AU  - Chiesa, Ana E.
AU  - Christodoulou, John
AU  - Đorđević, Maja
AU  - Desviat, Lourdes R.
AU  - Eliyahu, Aviva
AU  - Evers, Roeland A. F.
AU  - Fajkusova, Lena
AU  - Feillet, Francois
AU  - Bonfim-Freitas, Pedro E.
AU  - Gizewska, Maria
AU  - Gundorova, Polina
AU  - Karall, Daniela
AU  - Kneller, Katya
AU  - Kutsev, Sergey, I
AU  - Leuzzi, Vincenzo
AU  - Levy, Harvey L.
AU  - Lichter-Konecki, Uta
AU  - Muntau, Ania C.
AU  - Namour, Fares
AU  - Oltarzewski, Mariusz
AU  - Paras, Andrea
AU  - Perez, Belen
AU  - Polak, Emil
AU  - Polyakov, Alexander, V
AU  - Porta, Francesco
AU  - Rohrbach, Marianne
AU  - Scholl-Burgi, Sabine
AU  - Specola, Norma
AU  - Stojiljković, Maja
AU  - Shen, Nan
AU  - Santana-da Silva, Luiz C.
AU  - Skouma, Anastasia
AU  - van Spronsen, Francjan
AU  - Stoppioni, Vera
AU  - Thony, Beat
AU  - Trefz, Friedrich K.
AU  - Vockley, Jerry
AU  - Yu, Youngguo
AU  - Zschocke, Johannes
AU  - Hoffmann, Georg F.
AU  - Garbade, Sven F.
AU  - Blau, Nenad
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1314
AB  - 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.
PB  - Cell Press, Cambridge
T2  - American Journal of Human Genetics
T1  - The Genetic Landscape and Epidemiology of Phenylketonuria
EP  - 250
IS  - 2
SP  - 234
VL  - 107
DO  - 10.1016/j.ajhg.2020.06.006
ER  - 

@article{
author = "Hillert, Alicia and Anikster, Yair and Belanger-Quintana, Amaya and Burlina, Alberto and Burton, Barbara K. and Carducci, Carla and Chiesa, Ana E. and Christodoulou, John and Đorđević, Maja and Desviat, Lourdes R. and Eliyahu, Aviva and Evers, Roeland A. F. and Fajkusova, Lena and Feillet, Francois and Bonfim-Freitas, Pedro E. and Gizewska, Maria and Gundorova, Polina and Karall, Daniela and Kneller, Katya and Kutsev, Sergey, I and Leuzzi, Vincenzo and Levy, Harvey L. and Lichter-Konecki, Uta and Muntau, Ania C. and Namour, Fares and Oltarzewski, Mariusz and Paras, Andrea and Perez, Belen and Polak, Emil and Polyakov, Alexander, V and Porta, Francesco and Rohrbach, Marianne and Scholl-Burgi, Sabine and Specola, Norma and Stojiljković, Maja and Shen, Nan and Santana-da Silva, Luiz C. and Skouma, Anastasia and van Spronsen, Francjan and Stoppioni, Vera and Thony, Beat and Trefz, Friedrich K. and Vockley, Jerry and Yu, Youngguo and Zschocke, Johannes and Hoffmann, Georg F. and Garbade, Sven F. and Blau, Nenad",
year = "2020",
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.",
publisher = "Cell Press, Cambridge",
journal = "American Journal of Human Genetics",
title = "The Genetic Landscape and Epidemiology of Phenylketonuria",
pages = "250-234",
number = "2",
volume = "107",
doi = "10.1016/j.ajhg.2020.06.006"
}

Hillert, A., Anikster, Y., Belanger-Quintana, A., Burlina, A., Burton, B. K., Carducci, C., Chiesa, A. E., Christodoulou, J., Đorđević, M., Desviat, L. R., Eliyahu, A., Evers, R. A. F., Fajkusova, L., Feillet, F., Bonfim-Freitas, P. E., Gizewska, M., Gundorova, P., Karall, D., Kneller, K., Kutsev, S. I., Leuzzi, V., Levy, H. L., Lichter-Konecki, U., Muntau, A. C., Namour, F., Oltarzewski, M., Paras, A., Perez, B., Polak, E., Polyakov, A. V., Porta, F., Rohrbach, M., Scholl-Burgi, S., Specola, N., Stojiljković, M., Shen, N., Santana-da Silva, L. C., Skouma, A., van Spronsen, F., Stoppioni, V., Thony, B., Trefz, F. K., Vockley, J., Yu, Y., Zschocke, J., Hoffmann, G. F., Garbade, S. F.,& Blau, N.. (2020). The Genetic Landscape and Epidemiology of Phenylketonuria. in American Journal of Human Genetics
Cell Press, Cambridge., 107(2), 234-250.
https://doi.org/10.1016/j.ajhg.2020.06.006

Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, Chiesa AE, Christodoulou J, Đorđević M, Desviat LR, Eliyahu A, Evers RAF, Fajkusova L, Feillet F, Bonfim-Freitas PE, Gizewska M, Gundorova P, Karall D, Kneller K, Kutsev SI, Leuzzi V, Levy HL, Lichter-Konecki U, Muntau AC, Namour F, Oltarzewski M, Paras A, Perez B, Polak E, Polyakov AV, Porta F, Rohrbach M, Scholl-Burgi S, Specola N, Stojiljković M, Shen N, Santana-da Silva LC, Skouma A, van Spronsen F, Stoppioni V, Thony B, Trefz FK, Vockley J, Yu Y, Zschocke J, Hoffmann GF, Garbade SF, Blau N. The Genetic Landscape and Epidemiology of Phenylketonuria. in American Journal of Human Genetics. 2020;107(2):234-250.
doi:10.1016/j.ajhg.2020.06.006 .

Hillert, Alicia, Anikster, Yair, Belanger-Quintana, Amaya, Burlina, Alberto, Burton, Barbara K., Carducci, Carla, Chiesa, Ana E., Christodoulou, John, Đorđević, Maja, Desviat, Lourdes R., Eliyahu, Aviva, Evers, Roeland A. F., Fajkusova, Lena, Feillet, Francois, Bonfim-Freitas, Pedro E., Gizewska, Maria, Gundorova, Polina, Karall, Daniela, Kneller, Katya, Kutsev, Sergey, I, Leuzzi, Vincenzo, Levy, Harvey L., Lichter-Konecki, Uta, Muntau, Ania C., Namour, Fares, Oltarzewski, Mariusz, Paras, Andrea, Perez, Belen, Polak, Emil, Polyakov, Alexander, V, Porta, Francesco, Rohrbach, Marianne, Scholl-Burgi, Sabine, Specola, Norma, Stojiljković, Maja, Shen, Nan, Santana-da Silva, Luiz C., Skouma, Anastasia, van Spronsen, Francjan, Stoppioni, Vera, Thony, Beat, Trefz, Friedrich K., Vockley, Jerry, Yu, Youngguo, Zschocke, Johannes, Hoffmann, Georg F., Garbade, Sven F., Blau, Nenad, "The Genetic Landscape and Epidemiology of Phenylketonuria" in American Journal of Human Genetics, 107, no. 2 (2020):234-250,
https://doi.org/10.1016/j.ajhg.2020.06.006 . .