Trial reportEuropean journal of human genetics : EJHG2019
Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype-phenotype correlations in the largest cohort of patients with AKU.
Trial report in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone.RMD open · 2022Trial
- iTRAQ- and MRM-Based Proteomics Identify Early Injury Biomarkers for Primary Dysfunction After Liver Transplantation.Annals of transplantation · 2026Article
- Transcriptomics, Proteomics and Network Pharmacology Reveal the Mechanisms of Cantharidin-Induced Kidney Injury in Rats.Current issues in molecular biology · 2026Article
- Molecular characterization of Alkaptonuria in Brazilian patients.Molecular genetics and metabolism reports · 2026Article
- Molecular Analysis of the HGD Gene in 9 Families With Alkaptonuric Ochronosis in Iran and Identification of Two Novel Variants.Molecular genetics & genomic medicine · 2025Article
- Functional Characterization ofInternational journal of molecular sciences · 2025Article
- The iron metalloproteome of Pseudomonas aeruginosa under oxic and anoxic conditions.Metallomics : integrated biometal science · 2025Article
- Article
- Gene expression & biochemical analysis in alkaptonuria caused by a founder pathogenic variant across different age groups from India.The Indian journal of medical research · 2024Article
- A case of alkaptonuria presenting with unexplained dark-stained diapers and spurious hyperoxaluria and proteinuria due to homogentisic acid interference.Biochemia medica · 2024Article
- Joint replacement risk is markedly increased in alkaptonuria (AKU) in those with prior arthroplasty.Molecular genetics and metabolism reports · 2024Article
- Review
- Alkaptonuria.Nature reviews. Disease primers · 2024Review
- Exonic splicing code and coordination of divalent metals in proteins.Nucleic acids research · 2024Article
- Characterizing and predicting ccRCC-causing missense mutations in Von Hippel-Lindau disease.Human molecular genetics · 2024Article
- Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.PloS one · 2024Article
- AI-Driven Enhancements in Drug Screening and Optimization.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Bioinformatics Analysis Reveals Novel Differentially Expressed Genes Between Ectopic and Eutopic Endometrium in Women with Endometriosis.Journal of obstetrics and gynaecology of India · 2023Article
- Homogentisate 1,2-dioxygenase (HGD) gene variants in young Egyptian patients with alkaptonuria.Scientific reports · 2023Article
- Breakpoints characterisation of the genomic deletions identified by MLPA in alkaptonuria patients.European journal of human genetics : EJHG · 2023Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alkaptonuria (AKU) is a rare metabolic disorder caused by a deficient enzyme in the tyrosine degradation pathway, homogentisate 1,2-dioxygenase (HGD). In 172 AKU patients from 39 countries, we identified 28 novel variants of the HGD gene, which include three larger genomic deletions within this gene discovered via self-designed multiplex ligation-dependent probe amplification (MLPA) probes. In addition, using a reporter minigene assay, we provide evidence that three of eight tested variants potentially affecting splicing cause exon skipping or cryptic splice-site activation. Extensive bioinformatics analysis of novel missense variants, and of the entire HGD monomer, confirmed mCSM as an effective computational tool for evaluating possible enzyme inactivation mechanisms. For the first time for AKU, a genotype-phenotype correlation study was performed for the three most frequent HGD variants identified in the Suitability Of Nitisinone in Alkaptonuria 2 (SONIA2) study. We found a small but statistically significant difference in urinary homogentisic acid (HGA) excretion, corrected for dietary protein intake, between variants leading to 1% or >30% residual HGD activity. There was, interestingly, no difference in serum levels or absolute urinary excretion of HGA, or clinical symptoms, indicating that protein intake is more important than differences in HGD variants for the amounts of HGA that accumulate in the body of AKU patients.
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