ArticleJournal of human genetics2016
Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.
Article in Journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Spectrum of PAH gene mutations in 1547 phenylketonuria patients from Iran: a comprehensive systematic review.Metabolic brain disease · 2021Pooled it
- Molecular Genetic and Biochemical Characterization of Hyperphenylalaninemia Based on Expanded Neonatal Screening Data from 2023 to 2024 in the Russian Federation.International journal of molecular sciences · 2026Article
- The incidence rate and gene mutation characteristics of hyperphenylalaninemia in Yunnan Province, Southwest China.Orphanet journal of rare diseases · 2025Article
- Spectrum ofBiomedical reports · 2025Article
- Genomic profiling, implications for genotype-based treatment of 131 patients with phenylketonuria and characterization of novel p.Pro416Leu PAH variant.Scientific reports · 2025Article
- Incidence and disease spectrum of inherited metabolic diseases screened by tandem mass spectrometry in Huai'an from 2018 to 2024.Frontiers in pediatrics · 2025Article
- Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China.Molecular genetics & genomic medicine · 2023Article
- Diagnosis of inborn errors of metabolism within the expanded newborn screening in the Madrid region.JIMD reports · 2022Article
- An UpdatedGenes · 2021Article
- Phenylketonuria in Portugal: Genotype-phenotype correlations using molecular, biochemical, and haplotypic analyses.Molecular genetics & genomic medicine · 2021Article
- 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
- Expanded Newborn Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry in Suzhou, China: Disease Spectrum, Prevalence, Genetic Characteristics in a Chinese Population.Frontiers in genetics · 2019Article
- Spectrum of Phenylalanine Hydroxylase Gene Mutations in Hamadan and Lorestan Provinces of Iran and Their Associations with Variable Number of Tandem Repeat Alleles.Iranian journal of medical sciences · 2018Article
- Characterization of Phenyalanine Hydroxylase Gene Mutations in Chilean PKU Patients.JIMD reports · 2018Article
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Authors and funding
20 authors at 14 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.
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