SynthesisAmerican journal of human genetics1997
Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations.
Synthesis in American journal of human genetics, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- Spectrum of PAH gene mutations in 1547 phenylketonuria patients from Iran: a comprehensive systematic review.Metabolic brain disease · 2021Pooled it
- "MY PKU": increasing self-management in patients with phenylketonuria. A randomized controlled trial.Orphanet journal of rare diseases · 2011Trial
- Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes.Molecular genetics and metabolism · 2009Trial
- Phenylketonuria in adulthood: a collaborative study.Journal of inherited metabolic disease · 2002Trial
- Mapping the Severity of Phenylalanine Hydroxylase Deficiency.Journal of inherited metabolic disease · 2026Review
- Inherited metabolic epilepsies-established diseases, new approaches.Epilepsia open · 2024Review
- Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in theInternational journal of molecular sciences · 2024Article
- Allelic phenotype prediction of phenylketonuria based on the machine learning method.Human genomics · 2023Article
- A noncoding RNA modulator potentiates phenylalanine metabolism in mice.Science (New York, N.Y.) · 2021Article
- Oxidative stress in phenylketonuria-evidence from human studies and animal models, and possible implications for redox signaling.Metabolic brain disease · 2021Review
- Phenylketonuria in Portugal: Genotype-phenotype correlations using molecular, biochemical, and haplotypic analyses.Molecular genetics & genomic medicine · 2021Article
- Creatine plus pyruvate supplementation prevents oxidative stress and phosphotransfer network disturbances in the brain of rats subjected to chemically-induced phenylketonuria.Metabolic brain disease · 2019Article
- Genotype-phenotype correlations and BHMolecular genetics & genomic medicine · 2019Article
- Allelic phenotype values: a model for genotype-based phenotype prediction in phenylketonuria.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Unique aspects of sequence variant interpretation for inborn errors of metabolism (IEM): The ClinGen IEM Working Group and the Phenylalanine Hydroxylase Gene.Human mutation · 2018Article
- Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population.Journal of inherited metabolic disease · 2018Article
- Analysis of the genotype-phenotype correlation in patients with phenylketonuria in mainland China.Scientific reports · 2018Article
- Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria.Annals of nutrition & metabolism · 2017Article
- Missense variants in CFTR nucleotide-binding domains predict quantitative phenotypes associated with cystic fibrosis disease severity.Human molecular genetics · 2015Article
- Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.European journal of human genetics : EJHG · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We analyzed correlations between mutant genotypes at the human phenylalanine hydroxylase locus (gene symbol PAH) and the corresponding hyperphenylalaninemia (HPA) phenotypes (notably, phenylketonuria [OMIM 261600]). We used reports, both published and in the PAH Mutation Analysis Consortium Database, on 365 patients harboring 73 different PAH mutations in 161 different genotypes. HPA phenotypes were classified as phenylketonuria (PKU), variant PKU, and non-PKU HPA. By analysis both of homoallelic mutant genotypes and of "functionally hemizygous" heteroallelic genotypes, we characterized the phenotypic effect of 48 of the 73 different, largely missense mutations. Among those with consistent in vivo expression, 24 caused PKU, 3 caused variant PKU, and 10 caused non-PKU HPA. However, 11 mutations were inconsistent in their effect: 9 appeared in two different phenotype classes, and 2 (I65T and Y414C) appeared in all three classes. Seven mutations were inconsistent in phenotypic effect when in vitro (unit-protein) expression was compared with the corresponding in vivo phenotype (an emergent property). We conclude that the majority of PAH mutations confer a consistent phenotype and that this is concordant with their effects, when known, predicted from in vitro expression analysis. However, significant inconsistencies, both between in vitro and in vivo phenotypes and between different individuals with similar PAH genotypes, reveal that the HPA-phenotype is more complex than that predicted by Mendelian inheritance of alleles at the PAH locus.
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