The Genetic Landscape and Epidemiology of Phenylketonuria
2020
Аутори
Hillert, AliciaAnikster, 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
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 Aust...ralia (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.
Извор:
American Journal of Human Genetics, 2020, 107, 2, 234-250Издавач:
- Cell Press, Cambridge
Финансирање / пројекти:
- Fundacion Isabel Gemio-Fundacion La Caixa [LCF/PR/PR16/11110018]
- Regional Government of Madrid [B2017/BMD3721]
- NIH, United States [R01DK117916, R01NR016991]
- Victorian Government's Operational Infrastructure Support Program
- Dietmar Hopp Foundation, St. Leon-Rot
DOI: 10.1016/j.ajhg.2020.06.006
ISSN: 0002-9297
PubMed: 32668217
WoS: 000558491800006
Scopus: 2-s2.0-85088865157
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .