ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Allelic phenotype values: a model for genotype-based phenotype prediction in phenylketonuria.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients: Does It Improve Outcomes?Nutrients · 2022Pooled it
- Italian national consensus statement on management and pharmacological treatment of phenylketonuria.Orphanet journal of rare diseases · 2021Pooled it
- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Analysis ofInternational journal of molecular sciences · 2026Article
- Genetic landscape of phenylketonuria in Brazil.Orphanet journal of rare diseases · 2026Article
- Mapping the Severity of Phenylalanine Hydroxylase Deficiency.Journal of inherited metabolic disease · 2026Review
- Integrating Functional Consequence Annotation With PAH Allelic Phenotype Values Refines Prediction of Tetrahydrobiopterin Responsiveness.Journal of inherited metabolic disease · 2026Observational
- Sepiapterin: A Distinct, Dual Mechanism of Action that Leads to Potential Treatment Benefits Across the Spectrum of Phenylketonuria Disease Severities.Advances in therapy · 2026Article
- Benchmarking genetic birth prevalence estimates against newborn screening data.American journal of human genetics · 2026Article
- Genotype-phenotype correlations in phenylketonuria: PAH variants and BH4 responsiveness for treatment design.Human genomics · 2026Article
- Phenylalanine-tyrosine-catecholamine axis disorders: pathways, molecular diagnosis, therapeutics, and emerging translational monitoring technologies.Frontiers in molecular biosciences · 2026Review
- Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes.bioRxiv : the preprint server for biology · 2025Article
- Genotypic and phenotypic characteristics of Turkish patients with phenylalanine metabolism disorders.Metabolic brain disease · 2025Article
- Article
- An Oxford Nanopore Technologies-Based Sequencing Assay for Molecular Diagnosis of Phenylketonuria and Variant Frequencies in a Turkish Cohort.International journal of genomics · 2025Article
- Beginning of a new era of synthetic messenger RNA therapeutics: Comprehensive insights on mRNA drug design, development and applications.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Expanding diversity within phenylketonuria in ecuadorian patients: genetic analysis and literature review of newborn screenings.BMC pediatrics · 2024Review
- Development and validation of machine-learning models of diet management for hyperphenylalaninemia: a multicenter retrospective study.BMC medicine · 2024Observational
- Identified PAH V230A and PAH V230I mutations in a family with diverse clinical presentations.Clinical case reports · 2024Article
- [Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe 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.
methodsA total of 9336 PKU patients with 2589 different genotypes, carrying 588 variants, were investigated using an allelic phenotype value (APV) algorithm.
resultsWe 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).
conclusionsAPV and GPV are powerful tools to investigate genotype-phenotype associations, and can be used for genetic counselling of PKU families.
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