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| Verfasst von: | Garbade, Sven [VerfasserIn]  |
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| | Himmelreich, Nastassja [VerfasserIn] |
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| | Haas, Dorothea [VerfasserIn] |
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| | Trefz, Friedrich K. [VerfasserIn] |
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| | Hoffmann, Georg F. [VerfasserIn] |
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| | Burgard, Peter [VerfasserIn] |
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| | Blau, Nenad [VerfasserIn] |
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| Titel: | Allelic phenotype values |
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| Titelzusatz: | a model for genotype-based phenotype prediction in phenylketonuria |
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| Verf.angabe: | Sven F. Garbade, Nan Shen, Nastassja Himmelreich, Dorothea Haas, Friedrich K. Trefz, Georg F. Hoffmann, Peter Burgard, Nenad Blau |
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| Jahr: | 2019 |
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| Jahr des Originals: | 2018 |
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| Umfang: | 11 S. |
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| Fussnoten: | Published: 12 July 2018 ; Gesehen am 05.07.2019 |
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| Titel Quelle: | Enthalten in: Genetics in medicine |
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| Ort Quelle: | Amsterdam : Elsevier, 1998 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 21(2019), 3, Seite 580-590 |
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| ISSN Quelle: | 1530-0366 |
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| Abstract: | The nature of phenylalanine hydroxylase (PAH) variants determines residual enzyme activity, which modifies the clinical phenotype in phenylketonuria (PKU). We exploited the statistical power of a large genotype database to determine the relationship between genotype and phenotype in PKU. A total of 9336 PKU patients with 2589 different genotypes, carrying 588 variants, were investigated using an allelic phenotype value (APV) algorithm. We identified 251 0-variants encoding inactive PAH, and assigned APVs (0 = classic PKU; 5 = mild PKU; 10 = mild hyperphenylalaninaemia) to 88 variants in PAH-functional hemizygous patients. The genotypic phenotype values (GPVs) were set equal to the higher-APV allele, which was assumed to be dominant over the lower-APV allele and to determine the metabolic phenotype. GPVs for 8872 patients resulted in cut-off ranges of 0.0-2.7 for classic PKU, 2.8-6.6 for mild PKU and 6.7-10.0 for mild hyperphenylalaninaemia. Genotype-based phenotype prediction was 99.2% for classic PKU, 46.2% for mild PKU and 89.5% for mild hyperphenylalaninaemia. The relationships between known pretreatment blood phenylalanine levels and GPVs (n = 4217), as well as tetrahydrobiopterin responsiveness and GPVs (n = 3488), were significant (both P < 0.001). APV and GPV are powerful tools to investigate genotype-phenotype associations, and can be used for genetic counselling of PKU families. |
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| DOI: | doi:10.1038/s41436-018-0081-x |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1038/s41436-018-0081-x |
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| | Volltext: https://www.nature.com/articles/s41436-018-0081-x |
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| | DOI: https://doi.org/10.1038/s41436-018-0081-x |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1668689456 |
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| Verknüpfungen: | → Zeitschrift |
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